Coronaviral

[NikkiCFC 7,589]

How many people are vaccinated among these newly infected people in UK with this Delta variant? 

[Vesper 27,337]

21 minutes ago, NikkiCFC said:

How many people are vaccinated among these newly infected people in UK with this Delta variant? 

a lot, BUT a fair number either have had (speaking now of mRNA vaxxes only) only one vax, not two, OR they have one or even two doses of that dodgy AstraZeneca vax, which is absolutely a lesser vax efficacy-wise overall (it isn't even close) than the two mRNA (Pfizer and Moderna) vaccines.

The UK refusing to the proper length (21 days for Pfizer, 28 days for Moderna) of time between the first and second jabs is criminal. Fucking making people wait months between jabs in some cases is butchery. I would not expect less from the clown car show that is BoJo and the Tories. They almost always live up to asshattery expectations.

Edited July 4, 2021 by Vesper

[Jase 43,479]

Wahey. FINALLY got my first jab but now have to deal with a sore arm for a few days. lol

[Vesper 27,337]

Israel Sees Decline in Pfizer Vaccine Efficacy Rate, Ynet Reports

https://www.bloomberg.com/news/articles/2021-07-05/israel-sees-decline-in-pfizer-vaccine-efficacy-rate-ynet-says

The protection conferred by Pfizer Inc.’s vaccine against mild forms of Covid-19 appeared to wane after a few weeks in data garnered in Israel as the delta variant took hold, although the shot continued to shield users against severe illness.

The vaccine developed with BioNTech SE protected 64% of receivers against the illness between June 6 and early July as the government lifted restrictions, down from 94% between May 2 and June 5, the Ynet news website reported, citing Health Ministry numbers.

More importantly, those who were vaccinated remained far less likely to be hospitalized, with protection dropping only slightly to 93% from 98% in the period. The efficacy against serious illness was similar, according to the report.

The delta variant, which first emerged in India, is sparking concern as it spreads around the globe, providing a real-life test for vaccines and dashing hopes of recovery in air travel.

Dervila Keane, a spokeswoman at Pfizer, declined to comment on the data from Israel but she pointed to other research that shows continued protection against new mutations -- just slightly reduced in some cases. The evidence gathered so far suggests that the vaccine “will continue to protect against these variants,” she said.

New Curbs?

In Israel, where social curbs were lifted at the start of June, many of the new cases are among vaccinated people, according to Ynet. Last Friday, 55% of the newly infected had been vaccinated, the website said. As of July 4, there were 35 serious cases of coronavirus out of a population of 9.3 million, compared with 21 on June 19.

The government is considering reinstating additional restrictions after restoring a mandate to wear masks indoors in public spaces. Officials are also discussing whether to recommend a third dose of vaccine, the report said.

Pfizer CEO Albert Bourla has said people will “likely” need a third dose of vaccine within 12 months of getting fully protected.

Israel had one of the world’s most effective coronavirus inoculation drives and some 57% of the population is now fully vaccinated.

Edited July 5, 2021 by Vesper

[Vesper 27,337]

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

https://www.medrxiv.org/content/10.1101/2021.06.23.21259327v1

Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations.

Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines.

Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy.

Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351.

Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy.

Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

 

Introduction

The B.1.617.2 (Delta) variant that spread from India in March 2021 is now the dominant SARS-CoV-2 variant type in the United Kingdom ¹, replacing the B.1.1.7 (Alpha; “Kent”) variant and spreading rapidly across the globe.

The B.1.617.2 variant has been introduced into the UK on multiple occasions, most commonly associated with international travel from India where it has caused a large wave of COVID-19 infections and placed unprecedented demand on healthcare services ².

A key component of the UK response to COVID-19 is a campaign of mass vaccination, prioritizing the population by age and other risk groups. Vaccination began in December 2020 using the BNT162b2 mRNA vaccine (PfizerBioNTech). The ChAdOx1 adenovirus vectored vaccine (Oxford-AstraZeneca) was added from January 2021, with the mRNA-1273 vaccine (Moderna) available from April 2020.

Priority was given to administering the first dose of vaccine to as much of the UK population as possible, with second doses given within 12 weeks, in line with the guidance of the Joint Committee on Vaccination and Immunisation (JCVI). This delayed dosing strategy is now being challenged by the emergence of the B.1.617.2 lineage of SARS-CoV-2.

Recent data from Public Health England suggest that following exposure to this lineage, effectiveness of the BNT162b2 vaccine is reduced to 33.5% after one dose, and 87.9% following two doses ³. Further, the two-dose effectiveness of the ChAdOX1 vaccine is reduced to 59.8% following exposure to B.1.617.2 ³.

The early virus sequences detected in India were reported to have two key amino acid substitutions (L452R and E484Q) in the receptor-binding domain of the spike glycoprotein, the main immunodominant region and the region involved in ACE2 binding.

Accordingly, this resulted in the widespread usage of the “double mutant” misnomer, and initial designation as the B.1.617 Pango lineage. Availability of further sequence data led to the assignment of sub-lineages: B.1.617.1, B.1.617.2 and B.1.617.3, of which B.1.617.2 is now the dominant variant in the UK. The three lineages are characterized by the spike mutation L452R, whilst E484Q is present in B.1.617.1 and B.1.617.3 but not B.1.617.2.

The substitution L452R has been shown previously to reduce binding by several monoclonal antibodies ^{4, 5, 6, 7, 8} and convalescent plasma ⁶. Globally, L452R has emerged independently in several lineages since November/December 2020 suggesting a role in immune-evasion and/or virus adaptation ⁹. L452R is one of the defining mutations of the lineage B.1.427/B.1.429, a variant of interest (VOI) first identified in California and associated with reduced neutralisation titres with plasma from vaccinated or convalescent individuals ⁷.

Investigation of the effect of RBD mutations on binding of convalescent plasma by deep mutational scanning suggests the impact of E484Q is similar to that of E484K ¹⁰, which has been shown widely to diminish antibody binding, including those elicited by vaccination ^8, 11.

In this study, we investigated the neutralising capacity of sera from participants in the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study who had been vaccinated with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) or the ChAdOx1 adenovirus-vectored vaccine (Oxford-AstraZeneca) as part of the national deployed vaccine strategy.

 

Results

Characterisation of B.1.617.2 spike sequences

The B.1.617.2 lineage has spread rapidly across the globe following detection in India in late 2020. According to GISAID (https://www.gisaid.org - accessed on 10/06/2021), a total of 31,997 sequences (Europe = 24,606, Asia = 4,974, North America = 2,210, Oceania = 163, Africa = 36, South America = 8 ) have been assigned to lineage B.1.617.2, predominantly from the UK (n = 22,619; reflecting the large-scale UK sequencing effort).

The first B.1.617.2 sequence in the UK occurred on the 18^th March 2021 when the dominant UK lineage was B.1.1.7, and since the end of May 2021, B.1.617.2 accounts for the majority of SARS-CoV-2 samples sequenced (Fig. 1A). In order to make sure that our available reagents matched the majority of the circulating B.1.617.2 variants, we assessed the relative frequency of each spike mutation in all the available sequences (Fig. 1B).

Amino acid substitutions T19R, G142D, R158G, L452R, T478K, D614G, P681R, D950N and deletion Δ156-157 were present in the majority of the B.1.617.2 variants as chosen in the spike constructs used in our assays described below. The B.1.617.2 lineage continues to evolve, acquiring new mutations of concern such as K417N in the sub-lineage AY.1/B.1.617.2.1 (Fig. 1B).

Fig. 1.
Emergence of B.1.617.2 in the UK
(A). Weekly SARS-CoV-2 genome sequences of delta/B.1.617.2 (pink), alpha/B.1.1.7 (grey), and all other lineages (blue) in the UK, represented as a (stacked) percentage of all UK sequences that week, up to the week beginning 29th May 2021. Heatmap visualisation of spike mutations within UK B.1.617.2 SARS-CoV-2 genome sequences (B). Columns represent different amino acid mutations within the spike protein, whilst rows represent different specific combinations of spike mutations (“backbones”).

Only non-synonymous mutations (blue or pink for those with a known antigenic effect) and deletions (black) were considered, and only backbones observed 10 or more times are displayed. The observed frequency for each backbone is visualised in the Freq column whilst the antigenic column represents the total number of known antigenic mutations in the backbone; the backbone from the AY.1 lineage (derived from Nepal; containing mutations W258L and K417N) is also included (top row). The heatmap is hierarchically clustered based on the Euclidean distance between spike backbones (rows); backbones missing specific mutations/deletions could be indicative of Ns (failed amplicons) in the genome sequence at those sites rather than true absence.

Although each Pango lineage has a distinct mutation set, there are several similarities between the spike mutational profiles of the VOCs B.1.351, B.1.1.7 and B.1.617.2 (Fig. 2). They each have a deletion within the N-terminal domain supersite (NTDSS), at least one mutation in the receptor binding motif (RBM), and B.1.1.7 and B.1.617.2 each have a mutation at P681 within the furin cleavage site.

Fig. 2.
Spike mutations within variants of concern.
(A) Non-synonymous mutations (pink) and deletions (black) are shown for the variants of concern: B.1.1.7, B.1.351, B.1.617.1 and B.1.617.2, and P.1. Purple is used to distinguish secondary non-synonymous mutations at the same position, for example E484K (pink) and E484Q (purple). The region of the spike protein the mutation is located is highlighted on the top row; N-terminal domain (NTD), NTD antigenic supersite (NTDSS), receptor binding domain (RBD), receptor binding motif (RBM), furin cleavage site, S1 (NTD, NTDSS, RBD, RBM and furin are also in S1) and S2 subunits. Spike protein structure showing key B.1.617.1 and B.1.617.2 mutations (B).

Surface representation of spike homotrimer in open conformation with one upright RBD overlaid with ribbon representation (RCSB Protein Data Bank ID 6ZGG 21, with different monomers shown in black, pale blue and gold. Residues involved in B.1.617.1 and B.1.617.2 lineage defining substitutions or deletions are shown as red spheres on each of the three monomers and are labelled on the monomer with an upright RBD, shown in black. Scissors mark the approximate location of an exposed loop (residues 677-688), containing the furin cleavage site, and including residue 681, which is absent from the structure.

Antibody response post-vaccination

Sera were collected from 156 healthy individuals who had received one dose (n = 37) or two doses (n = 50) of BNT162b2 (Pfizer-BioNTech), or one dose (n= 50) or two doses (n = 18) of ChAdOx1 (Oxford/AstraZeneca) vaccines. Samples were screened initially by ELISA for reactivity with recombinant S1, RBD and N from the Wuhan-Hu-1 SARS-CoV-2 sequence.

Of those individuals vaccinated with BNT162b2, only one individual given a single dose (1/37) failed to mount a detectable antibody response against S1, all other samples were positive for reactivity against both S1 and RBD (Fig. 3A). In contrast, four individuals given a single dose (4/50) of ChAdOx1 failed to react with S1, although two of these samples bound the RBD antigen (Fig.3B).

All samples from individuals immunised with two doses of either BNT162b2 or ChAdOx1 reacted strongly against both S1 and RBD. Antibody reactivity (A405nm) was significantly higher following the second dose of either BNT162b2 (S1 and RBD, p<0.0001) or ChAdOx1 (S1 p=0.0006; RBD p=0.0014) compared with a single dose of the respective vaccines.

Moreover, reactivity against S1 was significantly greater in the groups immunised with either one (p=0.0152) or two (p=0.0145) doses of BNT162b2 in comparison with the groups immunised with one or two doses of ChAdOx1 respectively.

Similarly, reactivity against RBD was higher in samples from the groups immunised with either one (p=0.0029) or two (p=0.0018) doses of BNT162b2 in comparison with one or two doses of ChAdOx1 respectively. Eight individuals were identified with reactivity against SARS-CoV-2 N suggesting prior, undocumented exposure to SARS-CoV-2 or a related coronavirus. Exclusion of samples from these individuals did not affect the analyses (Table S1).

Figure 3.
Antibody response elicited by SARS-CoV-2 vaccines.
Sera from participants in the DOVE study were analysed by ELISA or pseudotype-based neutralisation assay. (A, ELISA reactivity in sera from individuals vaccinated with one or two doses of either BNT162b2 (A) or ChAdOx1 (B) was measured against recombinant S1 and RBD.

Each point represents A450nm, cut-offs for S1 and RBD respectively are denoted by dotted lines. (C-F) Neutralising antibodies from individuals vaccinated with one or two doses of BNT162b2 (C and D) or ChAdOx1 (E and F) were quantified against HIV(SARS-CoV-2) pseudotypes bearing the Wuhan-Hu-1, B.1.617.1, B.1.617.2 or B.1.351 spike glycoproteins.

Each point is the mean of three replicates, violin plot illustrates median plus quartiles. Mean titres were compared by one-way ANOVA. (G-J) Neutralising antibody titres were categorised based into the four viral variants against which they were determined; Wuhan-Hu-1 (G), B.1.617.1 (H), B.1.617.2 (I) or B.1.351 (J).

Samples were then subdivided into one or two doses of BNT162b2 or ChAdOx1 respectively for each variant and compared (one-way ANOVA, Tukey’s multiple comparison’s test). Vaccination with two doses of BNT162b2 induced significantly higher titres of antibody against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1 (**** p<0.0001, ** p=0.0011).

Neutralising antibody response

Neutralising antibodies were measured against HIV(SARS-CoV-2) pseudotypes expressing spike glycoproteins from either the vaccine sequence (Wuhan-Hu-1), or either B.1.617.1, B.1.617.2 or B.1.351. Antibody titres were estimated by interpolating the point at which infectivity (luciferase activity) was reduced by 50%.

Neutralizing antibodies were induced by vaccination with both the BNT162b2 (Fig.3 C, D) and ChAdOx1 (Fig.3 E, F) vaccines and two doses of either vaccine boosted the titre of neutralizing antibodies. Antibody titres were greatest against the Wuhan-Hu-1 spike glycoprotein and lower against the variants B.1.617.1, B.1.617.2 or B.1.351.

Samples from all individuals vaccinated with two doses of BNT162b2 neutralised Wuhan-Hu-1 efficiently (mean titre = 11473, n=50), however, mean antibody titres against the variants B.1.671.1, B.1.617.2 and B.1.351 were reduced by 7.77-fold, 11.30-fold and 9.56-fold respectively (significant, p<0.0001) (Table S1).

The mean antibody titre induced by vaccination with two doses of ChAdOx1 (mean titre = 1325.6, n=18) was significantly lower than that induced by two doses of BNT162b2 (mean titre = 11473).

After a single dose of ChAdOx1, 17 of 50 of vaccinated individuals (34%) had antibody titres ≤50. In comparison, only 5 of 37 individuals (13.5%) vaccinated with a single dose of BNT162b2 had antibody titres ≤50.

These data are consistent with ChAdOx1 inducing a weaker antibody response than BNT162b2 following primary immunisation. However, when the age distribution of the study cohorts was compared, it was notable that the age of participants vaccinated with the ChAdOx1 vaccine were on average 15 years older than those vaccinated with BNT162b2 (43 versus 58 respectively; Table S2), consistent with the shifting policy on age-group targeting mid-study.

The mean titre of antibodies detected in individuals with BNT162b2 against all the VOCs analysed was higher than those present in sera from individuals vaccinated with ChAdOx1 (Fig.3G-J). Vaccination with two doses of BNT162b2 induced significantly higher neutralising antibody titres against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1.

Discussion

The Delta variant B.1.617.2 that originated in India has rapidly become the dominant lineage in the UK. This variant is characterised by mutations in the genome that are associated with immune escape in other SARS-CoV-2 lineages.

In this study, we aimed to investigate the neutralisation profile of sera from participants in the DOVE deployed vaccine cohort study against B.1.617 sub-lineage variants. We compared neutralisation of B.1.617 variants with the original Wuhan-Hu-1 virus that has been used as the prototype for all currently deployed vaccines and the B.1.351 variant that originated in South Africa.

The B.1.351 variant has been shown to be associated with reduced neutralisation and breakthrough infection in clinical trials ¹². We aimed to quantify neutralisation profiles from sera obtained from recipients of the BNT162b2 and ChAdOx1 vaccines after one or two doses of vaccine, informing the UK strategy of maximising first dose rollout of vaccination in the population.

Our study showed that using the HIV (SARS-CoV-2) pseudotype-based system, neutralisation of the B.1.617.1, B.1.617.2 and B.1.351 variants was significantly lower in magnitude in comparison with the Wuhan-Hu-1 variant in participants vaccinated either with BNT162b2 or ChAdOx1 with an overall fold difference of 4.31, 5.11 and 6.29 respectively.

Two doses of BNT162b2 induced significantly higher neutralizing antibody titres against the Wuhan-Hu-1 and B.1.351 variants than one dose. A similar trend was noted in the B.1.617 lineage variants, although this did not reach statistical significance. In recipients of two doses of the Pfizer BNT162b2 vaccine, fold changes in neutralisation of the Wuhan-Hu-1 versus B.1.351, B.1.617.1 and B.1.617.2 variants were 7.77, 11.3 and 9.56-fold lower respectively.

These data are broadly in agreement with recent observations using sera from individuals vaccinated with BNT162b2 ¹³. The study showed that sera of vaccinated individuals were, on average, able to neutralise B.1.617.2 5.8-fold less efficiently than a virus circulating during the first wave of the pandemic, and with similar efficacy to B.1.351.

Both our study and Wall et al ¹³ used sera from “real world” vaccinated individuals rather than clinical trial participants and both showed a significant increase in neutralisation after two vaccine doses, despite employing two different neutralisation tests, a pseudotype-based assay and a live virus assay (based on fluorescent focus forming units).

In contrast, recent data from 20 sera collected from clinical trial participants vaccinated with BNT162b2 showed relatively similar levels of neutralising antibodies against B.1.617.1, B.1.617.2, B.1.618 (all first identified in India) and B.1.525 (first identified in Nigeria) using a live virus assay (plaque reduction assay)¹⁴.

Geometric mean plaque reduction neutralization titers against the variant viruses, particularly the B.1.617.1 variant, appeared lower than the titer against USA-WA1/2020 virus, but all sera tested neutralized the variant viruses at titres of at least 40 and displayed very uniform titres against each variant, as opposed to the spread of neutralising antibody levels observed in our study and in Wall et al ¹³. These discrepancies may be due to the source and number of the sera analysed or to the methodology used.

We also quantified neutralisation responses in recipients of the ChAdOx1 vaccine following one or two doses. In recipients of two doses of the ChAdOx1 vaccine, neutralisation of the Wuhan-Hu-1 versus B.1.351, B.1.617.1 and B.1.617.2 variants were 0.69, 4.01 and 1.48-fold lower respectively. However, the mean titre of antibodies detected in individuals with BNT162b2 against all the VOCs analysed was higher than those present in sera from individuals vaccinated with ChAdOx1.

Vaccination with two doses of BNT162b2 induced significantly higher neutralising antibody titres against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1. Further, the mean antibody titre induced by vaccination with two doses of ChAdOx1 was significantly lower than that induced by two doses of BNT162b2.

Due to vaccines being used in batches targeted at decreasing age groups in the UK, comparisons between neutralisation responses in recipients of the ChAdOx1 versus the BNT162b2, vaccines may be affected by the age differences between these groups (participants vaccinated with the ChAdOx1 were on average 15 years older than those vaccinated with BNT162b2 in our study) and will need further investigation as samples from broader populations of age-matched individuals become available.

In summary, we found that the B.1.617.2 variant, currently dominant in the UK is associated with significantly reduced neutralisation from vaccine sera obtained from recipients of the BNT162b2 or ChAdOx1 vaccines.

Neutralisation titres were higher following two doses of vaccine. These data are in keeping with recent vaccine effectiveness studies published by Public Health England (PHE) and Public Health Scotland (PHS), in which test negative case control designs were used to estimate the effectiveness of vaccination against symptomatic disease ^3, 15.

In the PHE study, data on all symptomatic sequenced cases of COVID-19 in England was used to estimate the proportion of cases with B.1.617.2 compared to the preceding B.1.1.7 variant by vaccination status. Effectiveness was found to be lower after one dose of vaccine with B.1.617.2 (33.5%) compared to B.1.1.7 (51.1%), with similar results for both vaccines.

After two doses of BNT162b2 vaccine, effectiveness reduced from 93.4% with B.1.1.7 to 87.9% with B.1.617.2. Following two doses of ChAdOx1, effectiveness reduced from 66.1% with B.1.1.7 to 59.8% with B.1.617.2. In addition, sequenced cases detected after one or two doses of vaccination had a higher odds of infection with B.1.617.2 compared to unvaccinated cases (OR 1.40; 95%CI: 1.13-1.75).

The PHS data from the EAVE-2 study employed S gene dropout status (a non-exclusive marker of the B.1.1.7 lineage but not the B.1.617.2 lineage) to estimate vaccine effectiveness. The BNT162b2 vaccine was found to be 92% in the S gene-negative group (inferred as B.1.1.7) versus 79% in the S gene-positive group (inferred as B.1.617.2).

The ChAdOx1 vaccine was reduced from 73% in S gene-negative cases versus 60% in S gene-positive ones. These data and ours suggest that pseudotype-based neutralisation assays are likely to reveal correlates of immunity to SARS-CoV-2 virus variants and further investigation to correlate neutralisation titres with vaccine failure is warranted.

The UK strategy for prioritisation of one-dose vaccination of the population with a second dose within 12 weeks is strongly associated with a significant reduction in deaths and hospitalisation associated with COVID-19 infection.

However, the emergence of the B.1.617.2 variant (or others with similar neutralisation profiles, such as B.1.351) may necessitate a modified approach, to counter the increase in infections observed with the B.1.617.2 variant in the UK.

More positively, despite this lower humoral response observed, hospitalisation rates of vaccinated people are remaining very low. This does indicate that the vaccine-elicited immune responses can moderate disease severity even in the face of a reduction in the antibody response.

High transmission rates of the B.1.617.2 variant in single-dose vaccine recipients or those previously infected with another variant may risk the evolution of vaccine-adapted variants. Further, reduction in titres over time may be expected to be associated with vaccine failure in those who have received two doses of vaccine.

Trials investigating whether a third dose of vaccine based on the original Wuhan-Hu-1 virus or adapted virus variants will help to prevent symptomatic infection with B.1.617.2 and future virus variants are underway (COV-BOOST https://www.covboost.org.uk/home).

Data Availability

All sequence data and metadata used in this work is shared via: The COG-UK website : https://www.cogconsortium.uk/data/ GISAID: https://www.gisaid.org/. All other source data will be made available upon the University of Glasgow Enlighten open-access research data server at http://researchdata.gla.ac.uk.

Materials and methods

Serum samples

Serum samples were collected from healthy volunteers participating in the COVID-19 Deployed Vaccine Cohort Study (DOVE), a cross-sectional cohort study to determine the immunogenicity of deployed COVID-19 vaccines against evolving SARS-CoV-2 variants. DOVE is a post-licensing cross-sectional cohort study of individuals vaccinated with deployed vaccines as part of the UK response to the COVID-19 pandemic.

Adult volunteers aged at least 18 years, were recruited into the observational study at 14 days post first or second dose of vaccine. Ethics: all participants gave informed consent to take part in the study. The study was approved by the North-West Liverpool Central Research Ethics Committee (REC reference 21/NW/0073).

Preparation of SARS-CoV-2 antigens for ELISA

S1 and RBD antigens were prepared as described previously ¹⁶. Briefly, the SARS-CoV-2 RBD and S1 constructs, spanning SARS-CoV-2 S (UniProt ID P59594) residues 319-541 (RVQPT…KCVNF) and 1-530 (MFVFL…GPKKS), respectively, were produced with C-terminal twin Strep tags in the mammalian expression vector pQ-3C-2xStrep38.

A signal peptide from immunoglobulin kappa gene product (METDTLLLWVLLLWVPGSTGD) was used to direct secretion of the RBD construct. Proteins were produced by transient expression in Expi293F cells growing in FreeStyle 293 medium. Conditioned media containing secreted proteins were harvested at two timepoints, 3-4 and 6-8 days post-transfection.

Twin Strep-tagged proteins were captured on Streptactin XT (IBA LifeSciences), eluted, and then purified to homogeneity by size exclusion chromatography through Superdex 200 (GE Healthcare). Purified SARS CoV2 antigens, concentrated to 1-5 mg/ml by ultrafiltration were aliquoted and snap-frozen in liquid nitrogen prior to storage at -80°C.

ELISA for SARS-CoV-2 antibodies

ELISAs for SARS-CoV-2 antibodies were performed as described previously ¹⁷. Briefly, 96-well plates were coated overnight at 4°C with purified SARS-CoV-2 antigens in phosphate-buffered saline (PBS).

Wells were blocked for 1 hr at room temperature in blocking buffer consisting of PBS with 0.05% Tween 20 (PBS/Tween) and 1X casein (Vector labs., Peterborough, UK). Plates were then washed 3x in PBS/Tween prior to incubation with 50µL of each serum sample diluted 1:100 in blocking buffer.

Each plate included two pooled negative controls and two pooled positive controls. Sera were incubated for 1 hour at room temperature. Plates were then washed 3x with PBS/Tween, before incubation for 1 hour with horseradish peroxidase (HRP)-conjugated rabbit anti-human IgG (Bethyl labs., Cambridge Bioscience, Cambridge, UK) diluted 1:2500 in blocking buffer.

Plates were washed a further 3x in PBS/Tween before addition of the 3,3’,5,5’-tetramethylbenzidine (TMB) liquid substrate (Sigma Aldrich, Merck, Dorset, UK). Colour development was allowed to proceed for 10 minutes before the addition of 1M H2SO4 stop solution, at which point the absorbance was determined at 450nm on a Multiskan FC plate reader. Full validation of the S1 and RBD ELISA has been described previously¹⁷.

Measurement of neutralising antibody activity using viral pseudotypes

HEK293, HEK293T, and 293-ACE2 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal bovine serum, 200mM L-glutamine, 100µg/ml streptomycin and 100 IU/ml penicillin. HEK293T cells were transfected with the appropriate SARS-CoV-2 S gene expression vector (wild type or variant) in conjunction with p8.91 ¹⁸ and pCSFLW ¹⁹ using polyethylenimine (PEI, Polysciences, Warrington, USA). HIV (SARS-CoV-2) pseudotypes containing supernatants were harvested 48 hours post-transfection, aliquoted and frozen at -80°C prior to use.

The SARS-CoV-2 spike glycoprotein expression construct for Wuhan-Hu-1 was obtained from Nigel Temperton, University of Kent. The S gene of B.1.351 (South Africa) was based on the codon-optimised sequence of the Wuhan-Hu-1 expression construct, synthesised by Genscript (Netherlands) and sub-cloned into the pCDNA6 expression vector. S gene constructs bearing the B.1.617.1 and B.1.617.2 S genes were based on the codon-optimised spike sequence of SARS-CoV-2 ²⁰ and generated using the QuikChange Multi Site-Directed Mutagenesis Kit (Agilent, USA).

Constructs bore the following mutations relative to the Wuhan-Hu-1 sequence (GenBank: MN908947 ) B.1.351 – D80A, D215G, L241-243del, K417N, E484K, N501Y, D614G, A701V; B.1.617.1 – T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H; B.1.617.2 – T19R, G142D, E156del, F157del, R158G, L452R, T478K, D614G, P681R, D950N. 293-ACE2 target cells ¹⁷ were maintained in complete DMEM supplemented with 2µg/ml puromycin.

Neutralising activity in each sample was measured by a serial dilution approach. Each sample was serially diluted in triplicate from 1:50 to 1:36450 in complete DMEM prior to incubation with HIV (SARS-CoV-2) pseudotypes, incubated for 1 hour, and plated onto 239-ACE2 target cells.

After 48-72 hours, luciferase activity was quantified by the addition of Steadylite Plus chemiluminescence substrate and analysis on a Perkin Elmer EnSight multimode plate reader (Perkin Elmer, Beaconsfield, UK). Antibody titre was then estimated by interpolating the point at which infectivity had been reduced to 90% of the value for the no serum control samples.

 

Edited July 5, 2021 by Vesper

[Vesper 27,337]

11 minutes ago, Vesper said:

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

https://www.medrxiv.org/content/10.1101/2021.06.23.21259327v1

Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations.

Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines.

Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy.

Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351.

Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy.

Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

 

Introduction

The B.1.617.2 (Delta) variant that spread from India in March 2021 is now the dominant SARS-CoV-2 variant type in the United Kingdom ¹, replacing the B.1.1.7 (Alpha; “Kent”) variant and spreading rapidly across the globe.

The B.1.617.2 variant has been introduced into the UK on multiple occasions, most commonly associated with international travel from India where it has caused a large wave of COVID-19 infections and placed unprecedented demand on healthcare services ².

A key component of the UK response to COVID-19 is a campaign of mass vaccination, prioritizing the population by age and other risk groups. Vaccination began in December 2020 using the BNT162b2 mRNA vaccine (PfizerBioNTech). The ChAdOx1 adenovirus vectored vaccine (Oxford-AstraZeneca) was added from January 2021, with the mRNA-1273 vaccine (Moderna) available from April 2020.

Priority was given to administering the first dose of vaccine to as much of the UK population as possible, with second doses given within 12 weeks, in line with the guidance of the Joint Committee on Vaccination and Immunisation (JCVI). This delayed dosing strategy is now being challenged by the emergence of the B.1.617.2 lineage of SARS-CoV-2.

Recent data from Public Health England suggest that following exposure to this lineage, effectiveness of the BNT162b2 vaccine is reduced to 33.5% after one dose, and 87.9% following two doses ³. Further, the two-dose effectiveness of the ChAdOX1 vaccine is reduced to 59.8% following exposure to B.1.617.2 ³.

The early virus sequences detected in India were reported to have two key amino acid substitutions (L452R and E484Q) in the receptor-binding domain of the spike glycoprotein, the main immunodominant region and the region involved in ACE2 binding.

Accordingly, this resulted in the widespread usage of the “double mutant” misnomer, and initial designation as the B.1.617 Pango lineage. Availability of further sequence data led to the assignment of sub-lineages: B.1.617.1, B.1.617.2 and B.1.617.3, of which B.1.617.2 is now the dominant variant in the UK. The three lineages are characterized by the spike mutation L452R, whilst E484Q is present in B.1.617.1 and B.1.617.3 but not B.1.617.2.

The substitution L452R has been shown previously to reduce binding by several monoclonal antibodies ^{4, 5, 6, 7, 8} and convalescent plasma ⁶. Globally, L452R has emerged independently in several lineages since November/December 2020 suggesting a role in immune-evasion and/or virus adaptation ⁹. L452R is one of the defining mutations of the lineage B.1.427/B.1.429, a variant of interest (VOI) first identified in California and associated with reduced neutralisation titres with plasma from vaccinated or convalescent individuals ⁷.

Investigation of the effect of RBD mutations on binding of convalescent plasma by deep mutational scanning suggests the impact of E484Q is similar to that of E484K ¹⁰, which has been shown widely to diminish antibody binding, including those elicited by vaccination ^8, 11.

In this study, we investigated the neutralising capacity of sera from participants in the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study who had been vaccinated with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) or the ChAdOx1 adenovirus-vectored vaccine (Oxford-AstraZeneca) as part of the national deployed vaccine strategy.

 

Results

Characterisation of B.1.617.2 spike sequences

The B.1.617.2 lineage has spread rapidly across the globe following detection in India in late 2020. According to GISAID (https://www.gisaid.org - accessed on 10/06/2021), a total of 31,997 sequences (Europe = 24,606, Asia = 4,974, North America = 2,210, Oceania = 163, Africa = 36, South America = 8 ) have been assigned to lineage B.1.617.2, predominantly from the UK (n = 22,619; reflecting the large-scale UK sequencing effort).

The first B.1.617.2 sequence in the UK occurred on the 18^th March 2021 when the dominant UK lineage was B.1.1.7, and since the end of May 2021, B.1.617.2 accounts for the majority of SARS-CoV-2 samples sequenced (Fig. 1A). In order to make sure that our available reagents matched the majority of the circulating B.1.617.2 variants, we assessed the relative frequency of each spike mutation in all the available sequences (Fig. 1B).

Amino acid substitutions T19R, G142D, R158G, L452R, T478K, D614G, P681R, D950N and deletion Δ156-157 were present in the majority of the B.1.617.2 variants as chosen in the spike constructs used in our assays described below. The B.1.617.2 lineage continues to evolve, acquiring new mutations of concern such as K417N in the sub-lineage AY.1/B.1.617.2.1 (Fig. 1B).

Fig. 1.
Emergence of B.1.617.2 in the UK
(A). Weekly SARS-CoV-2 genome sequences of delta/B.1.617.2 (pink), alpha/B.1.1.7 (grey), and all other lineages (blue) in the UK, represented as a (stacked) percentage of all UK sequences that week, up to the week beginning 29th May 2021. Heatmap visualisation of spike mutations within UK B.1.617.2 SARS-CoV-2 genome sequences (B). Columns represent different amino acid mutations within the spike protein, whilst rows represent different specific combinations of spike mutations (“backbones”).

Only non-synonymous mutations (blue or pink for those with a known antigenic effect) and deletions (black) were considered, and only backbones observed 10 or more times are displayed. The observed frequency for each backbone is visualised in the Freq column whilst the antigenic column represents the total number of known antigenic mutations in the backbone; the backbone from the AY.1 lineage (derived from Nepal; containing mutations W258L and K417N) is also included (top row). The heatmap is hierarchically clustered based on the Euclidean distance between spike backbones (rows); backbones missing specific mutations/deletions could be indicative of Ns (failed amplicons) in the genome sequence at those sites rather than true absence.

Although each Pango lineage has a distinct mutation set, there are several similarities between the spike mutational profiles of the VOCs B.1.351, B.1.1.7 and B.1.617.2 (Fig. 2). They each have a deletion within the N-terminal domain supersite (NTDSS), at least one mutation in the receptor binding motif (RBM), and B.1.1.7 and B.1.617.2 each have a mutation at P681 within the furin cleavage site.

Fig. 2.
Spike mutations within variants of concern.
(A) Non-synonymous mutations (pink) and deletions (black) are shown for the variants of concern: B.1.1.7, B.1.351, B.1.617.1 and B.1.617.2, and P.1. Purple is used to distinguish secondary non-synonymous mutations at the same position, for example E484K (pink) and E484Q (purple). The region of the spike protein the mutation is located is highlighted on the top row; N-terminal domain (NTD), NTD antigenic supersite (NTDSS), receptor binding domain (RBD), receptor binding motif (RBM), furin cleavage site, S1 (NTD, NTDSS, RBD, RBM and furin are also in S1) and S2 subunits. Spike protein structure showing key B.1.617.1 and B.1.617.2 mutations (B).

Surface representation of spike homotrimer in open conformation with one upright RBD overlaid with ribbon representation (RCSB Protein Data Bank ID 6ZGG 21, with different monomers shown in black, pale blue and gold. Residues involved in B.1.617.1 and B.1.617.2 lineage defining substitutions or deletions are shown as red spheres on each of the three monomers and are labelled on the monomer with an upright RBD, shown in black. Scissors mark the approximate location of an exposed loop (residues 677-688), containing the furin cleavage site, and including residue 681, which is absent from the structure.

Antibody response post-vaccination

Sera were collected from 156 healthy individuals who had received one dose (n = 37) or two doses (n = 50) of BNT162b2 (Pfizer-BioNTech), or one dose (n= 50) or two doses (n = 18) of ChAdOx1 (Oxford/AstraZeneca) vaccines. Samples were screened initially by ELISA for reactivity with recombinant S1, RBD and N from the Wuhan-Hu-1 SARS-CoV-2 sequence.

Of those individuals vaccinated with BNT162b2, only one individual given a single dose (1/37) failed to mount a detectable antibody response against S1, all other samples were positive for reactivity against both S1 and RBD (Fig. 3A). In contrast, four individuals given a single dose (4/50) of ChAdOx1 failed to react with S1, although two of these samples bound the RBD antigen (Fig.3B).

All samples from individuals immunised with two doses of either BNT162b2 or ChAdOx1 reacted strongly against both S1 and RBD. Antibody reactivity (A405nm) was significantly higher following the second dose of either BNT162b2 (S1 and RBD, p<0.0001) or ChAdOx1 (S1 p=0.0006; RBD p=0.0014) compared with a single dose of the respective vaccines.

Moreover, reactivity against S1 was significantly greater in the groups immunised with either one (p=0.0152) or two (p=0.0145) doses of BNT162b2 in comparison with the groups immunised with one or two doses of ChAdOx1 respectively.

Similarly, reactivity against RBD was higher in samples from the groups immunised with either one (p=0.0029) or two (p=0.0018) doses of BNT162b2 in comparison with one or two doses of ChAdOx1 respectively. Eight individuals were identified with reactivity against SARS-CoV-2 N suggesting prior, undocumented exposure to SARS-CoV-2 or a related coronavirus. Exclusion of samples from these individuals did not affect the analyses (Table S1).

Figure 3.
Antibody response elicited by SARS-CoV-2 vaccines.
Sera from participants in the DOVE study were analysed by ELISA or pseudotype-based neutralisation assay. (A, ELISA reactivity in sera from individuals vaccinated with one or two doses of either BNT162b2 (A) or ChAdOx1 (B) was measured against recombinant S1 and RBD.

Each point represents A450nm, cut-offs for S1 and RBD respectively are denoted by dotted lines. (C-F) Neutralising antibodies from individuals vaccinated with one or two doses of BNT162b2 (C and D) or ChAdOx1 (E and F) were quantified against HIV(SARS-CoV-2) pseudotypes bearing the Wuhan-Hu-1, B.1.617.1, B.1.617.2 or B.1.351 spike glycoproteins.

Each point is the mean of three replicates, violin plot illustrates median plus quartiles. Mean titres were compared by one-way ANOVA. (G-J) Neutralising antibody titres were categorised based into the four viral variants against which they were determined; Wuhan-Hu-1 (G), B.1.617.1 (H), B.1.617.2 (I) or B.1.351 (J).

Samples were then subdivided into one or two doses of BNT162b2 or ChAdOx1 respectively for each variant and compared (one-way ANOVA, Tukey’s multiple comparison’s test). Vaccination with two doses of BNT162b2 induced significantly higher titres of antibody against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1 (**** p<0.0001, ** p=0.0011).

Neutralising antibody response

Neutralising antibodies were measured against HIV(SARS-CoV-2) pseudotypes expressing spike glycoproteins from either the vaccine sequence (Wuhan-Hu-1), or either B.1.617.1, B.1.617.2 or B.1.351. Antibody titres were estimated by interpolating the point at which infectivity (luciferase activity) was reduced by 50%.

Neutralizing antibodies were induced by vaccination with both the BNT162b2 (Fig.3 C, D) and ChAdOx1 (Fig.3 E, F) vaccines and two doses of either vaccine boosted the titre of neutralizing antibodies. Antibody titres were greatest against the Wuhan-Hu-1 spike glycoprotein and lower against the variants B.1.617.1, B.1.617.2 or B.1.351.

Samples from all individuals vaccinated with two doses of BNT162b2 neutralised Wuhan-Hu-1 efficiently (mean titre = 11473, n=50), however, mean antibody titres against the variants B.1.671.1, B.1.617.2 and B.1.351 were reduced by 7.77-fold, 11.30-fold and 9.56-fold respectively (significant, p<0.0001) (Table S1).

The mean antibody titre induced by vaccination with two doses of ChAdOx1 (mean titre = 1325.6, n=18) was significantly lower than that induced by two doses of BNT162b2 (mean titre = 11473).

After a single dose of ChAdOx1, 17 of 50 of vaccinated individuals (34%) had antibody titres ≤50. In comparison, only 5 of 37 individuals (13.5%) vaccinated with a single dose of BNT162b2 had antibody titres ≤50.

These data are consistent with ChAdOx1 inducing a weaker antibody response than BNT162b2 following primary immunisation. However, when the age distribution of the study cohorts was compared, it was notable that the age of participants vaccinated with the ChAdOx1 vaccine were on average 15 years older than those vaccinated with BNT162b2 (43 versus 58 respectively; Table S2), consistent with the shifting policy on age-group targeting mid-study.

The mean titre of antibodies detected in individuals with BNT162b2 against all the VOCs analysed was higher than those present in sera from individuals vaccinated with ChAdOx1 (Fig.3G-J). Vaccination with two doses of BNT162b2 induced significantly higher neutralising antibody titres against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1.

Discussion

The Delta variant B.1.617.2 that originated in India has rapidly become the dominant lineage in the UK. This variant is characterised by mutations in the genome that are associated with immune escape in other SARS-CoV-2 lineages.

In this study, we aimed to investigate the neutralisation profile of sera from participants in the DOVE deployed vaccine cohort study against B.1.617 sub-lineage variants. We compared neutralisation of B.1.617 variants with the original Wuhan-Hu-1 virus that has been used as the prototype for all currently deployed vaccines and the B.1.351 variant that originated in South Africa.

The B.1.351 variant has been shown to be associated with reduced neutralisation and breakthrough infection in clinical trials ¹². We aimed to quantify neutralisation profiles from sera obtained from recipients of the BNT162b2 and ChAdOx1 vaccines after one or two doses of vaccine, informing the UK strategy of maximising first dose rollout of vaccination in the population.

Our study showed that using the HIV (SARS-CoV-2) pseudotype-based system, neutralisation of the B.1.617.1, B.1.617.2 and B.1.351 variants was significantly lower in magnitude in comparison with the Wuhan-Hu-1 variant in participants vaccinated either with BNT162b2 or ChAdOx1 with an overall fold difference of 4.31, 5.11 and 6.29 respectively.

Two doses of BNT162b2 induced significantly higher neutralizing antibody titres against the Wuhan-Hu-1 and B.1.351 variants than one dose. A similar trend was noted in the B.1.617 lineage variants, although this did not reach statistical significance. In recipients of two doses of the Pfizer BNT162b2 vaccine, fold changes in neutralisation of the Wuhan-Hu-1 versus B.1.351, B.1.617.1 and B.1.617.2 variants were 7.77, 11.3 and 9.56-fold lower respectively.

These data are broadly in agreement with recent observations using sera from individuals vaccinated with BNT162b2 ¹³. The study showed that sera of vaccinated individuals were, on average, able to neutralise B.1.617.2 5.8-fold less efficiently than a virus circulating during the first wave of the pandemic, and with similar efficacy to B.1.351.

Both our study and Wall et al ¹³ used sera from “real world” vaccinated individuals rather than clinical trial participants and both showed a significant increase in neutralisation after two vaccine doses, despite employing two different neutralisation tests, a pseudotype-based assay and a live virus assay (based on fluorescent focus forming units).

In contrast, recent data from 20 sera collected from clinical trial participants vaccinated with BNT162b2 showed relatively similar levels of neutralising antibodies against B.1.617.1, B.1.617.2, B.1.618 (all first identified in India) and B.1.525 (first identified in Nigeria) using a live virus assay (plaque reduction assay)¹⁴.

Geometric mean plaque reduction neutralization titers against the variant viruses, particularly the B.1.617.1 variant, appeared lower than the titer against USA-WA1/2020 virus, but all sera tested neutralized the variant viruses at titres of at least 40 and displayed very uniform titres against each variant, as opposed to the spread of neutralising antibody levels observed in our study and in Wall et al ¹³. These discrepancies may be due to the source and number of the sera analysed or to the methodology used.

We also quantified neutralisation responses in recipients of the ChAdOx1 vaccine following one or two doses. In recipients of two doses of the ChAdOx1 vaccine, neutralisation of the Wuhan-Hu-1 versus B.1.351, B.1.617.1 and B.1.617.2 variants were 0.69, 4.01 and 1.48-fold lower respectively. However, the mean titre of antibodies detected in individuals with BNT162b2 against all the VOCs analysed was higher than those present in sera from individuals vaccinated with ChAdOx1.

Vaccination with two doses of BNT162b2 induced significantly higher neutralising antibody titres against the Wuhan-Hu-1 virus than either one dose of BNT162b2, or two doses of ChAdOx1. Further, the mean antibody titre induced by vaccination with two doses of ChAdOx1 was significantly lower than that induced by two doses of BNT162b2.

Due to vaccines being used in batches targeted at decreasing age groups in the UK, comparisons between neutralisation responses in recipients of the ChAdOx1 versus the BNT162b2, vaccines may be affected by the age differences between these groups (participants vaccinated with the ChAdOx1 were on average 15 years older than those vaccinated with BNT162b2 in our study) and will need further investigation as samples from broader populations of age-matched individuals become available.

In summary, we found that the B.1.617.2 variant, currently dominant in the UK is associated with significantly reduced neutralisation from vaccine sera obtained from recipients of the BNT162b2 or ChAdOx1 vaccines.

Neutralisation titres were higher following two doses of vaccine. These data are in keeping with recent vaccine effectiveness studies published by Public Health England (PHE) and Public Health Scotland (PHS), in which test negative case control designs were used to estimate the effectiveness of vaccination against symptomatic disease ^3, 15.

In the PHE study, data on all symptomatic sequenced cases of COVID-19 in England was used to estimate the proportion of cases with B.1.617.2 compared to the preceding B.1.1.7 variant by vaccination status. Effectiveness was found to be lower after one dose of vaccine with B.1.617.2 (33.5%) compared to B.1.1.7 (51.1%), with similar results for both vaccines.

After two doses of BNT162b2 vaccine, effectiveness reduced from 93.4% with B.1.1.7 to 87.9% with B.1.617.2. Following two doses of ChAdOx1, effectiveness reduced from 66.1% with B.1.1.7 to 59.8% with B.1.617.2. In addition, sequenced cases detected after one or two doses of vaccination had a higher odds of infection with B.1.617.2 compared to unvaccinated cases (OR 1.40; 95%CI: 1.13-1.75).

The PHS data from the EAVE-2 study employed S gene dropout status (a non-exclusive marker of the B.1.1.7 lineage but not the B.1.617.2 lineage) to estimate vaccine effectiveness. The BNT162b2 vaccine was found to be 92% in the S gene-negative group (inferred as B.1.1.7) versus 79% in the S gene-positive group (inferred as B.1.617.2).

The ChAdOx1 vaccine was reduced from 73% in S gene-negative cases versus 60% in S gene-positive ones. These data and ours suggest that pseudotype-based neutralisation assays are likely to reveal correlates of immunity to SARS-CoV-2 virus variants and further investigation to correlate neutralisation titres with vaccine failure is warranted.

The UK strategy for prioritisation of one-dose vaccination of the population with a second dose within 12 weeks is strongly associated with a significant reduction in deaths and hospitalisation associated with COVID-19 infection.

However, the emergence of the B.1.617.2 variant (or others with similar neutralisation profiles, such as B.1.351) may necessitate a modified approach, to counter the increase in infections observed with the B.1.617.2 variant in the UK.

More positively, despite this lower humoral response observed, hospitalisation rates of vaccinated people are remaining very low. This does indicate that the vaccine-elicited immune responses can moderate disease severity even in the face of a reduction in the antibody response.

High transmission rates of the B.1.617.2 variant in single-dose vaccine recipients or those previously infected with another variant may risk the evolution of vaccine-adapted variants. Further, reduction in titres over time may be expected to be associated with vaccine failure in those who have received two doses of vaccine.

Trials investigating whether a third dose of vaccine based on the original Wuhan-Hu-1 virus or adapted virus variants will help to prevent symptomatic infection with B.1.617.2 and future virus variants are underway (COV-BOOST https://www.covboost.org.uk/home).

Data Availability

All sequence data and metadata used in this work is shared via: The COG-UK website : https://www.cogconsortium.uk/data/ GISAID: https://www.gisaid.org/. All other source data will be made available upon the University of Glasgow Enlighten open-access research data server at http://researchdata.gla.ac.uk.

Materials and methods

Serum samples

Serum samples were collected from healthy volunteers participating in the COVID-19 Deployed Vaccine Cohort Study (DOVE), a cross-sectional cohort study to determine the immunogenicity of deployed COVID-19 vaccines against evolving SARS-CoV-2 variants. DOVE is a post-licensing cross-sectional cohort study of individuals vaccinated with deployed vaccines as part of the UK response to the COVID-19 pandemic.

Adult volunteers aged at least 18 years, were recruited into the observational study at 14 days post first or second dose of vaccine. Ethics: all participants gave informed consent to take part in the study. The study was approved by the North-West Liverpool Central Research Ethics Committee (REC reference 21/NW/0073).

Preparation of SARS-CoV-2 antigens for ELISA

S1 and RBD antigens were prepared as described previously ¹⁶. Briefly, the SARS-CoV-2 RBD and S1 constructs, spanning SARS-CoV-2 S (UniProt ID P59594) residues 319-541 (RVQPT…KCVNF) and 1-530 (MFVFL…GPKKS), respectively, were produced with C-terminal twin Strep tags in the mammalian expression vector pQ-3C-2xStrep38.

A signal peptide from immunoglobulin kappa gene product (METDTLLLWVLLLWVPGSTGD) was used to direct secretion of the RBD construct. Proteins were produced by transient expression in Expi293F cells growing in FreeStyle 293 medium. Conditioned media containing secreted proteins were harvested at two timepoints, 3-4 and 6-8 days post-transfection.

Twin Strep-tagged proteins were captured on Streptactin XT (IBA LifeSciences), eluted, and then purified to homogeneity by size exclusion chromatography through Superdex 200 (GE Healthcare). Purified SARS CoV2 antigens, concentrated to 1-5 mg/ml by ultrafiltration were aliquoted and snap-frozen in liquid nitrogen prior to storage at -80°C.

ELISA for SARS-CoV-2 antibodies

ELISAs for SARS-CoV-2 antibodies were performed as described previously ¹⁷. Briefly, 96-well plates were coated overnight at 4°C with purified SARS-CoV-2 antigens in phosphate-buffered saline (PBS).

Wells were blocked for 1 hr at room temperature in blocking buffer consisting of PBS with 0.05% Tween 20 (PBS/Tween) and 1X casein (Vector labs., Peterborough, UK). Plates were then washed 3x in PBS/Tween prior to incubation with 50µL of each serum sample diluted 1:100 in blocking buffer.

Each plate included two pooled negative controls and two pooled positive controls. Sera were incubated for 1 hour at room temperature. Plates were then washed 3x with PBS/Tween, before incubation for 1 hour with horseradish peroxidase (HRP)-conjugated rabbit anti-human IgG (Bethyl labs., Cambridge Bioscience, Cambridge, UK) diluted 1:2500 in blocking buffer.

Plates were washed a further 3x in PBS/Tween before addition of the 3,3’,5,5’-tetramethylbenzidine (TMB) liquid substrate (Sigma Aldrich, Merck, Dorset, UK). Colour development was allowed to proceed for 10 minutes before the addition of 1M H2SO4 stop solution, at which point the absorbance was determined at 450nm on a Multiskan FC plate reader. Full validation of the S1 and RBD ELISA has been described previously¹⁷.

Measurement of neutralising antibody activity using viral pseudotypes

HEK293, HEK293T, and 293-ACE2 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal bovine serum, 200mM L-glutamine, 100µg/ml streptomycin and 100 IU/ml penicillin. HEK293T cells were transfected with the appropriate SARS-CoV-2 S gene expression vector (wild type or variant) in conjunction with p8.91 ¹⁸ and pCSFLW ¹⁹ using polyethylenimine (PEI, Polysciences, Warrington, USA). HIV (SARS-CoV-2) pseudotypes containing supernatants were harvested 48 hours post-transfection, aliquoted and frozen at -80°C prior to use.

The SARS-CoV-2 spike glycoprotein expression construct for Wuhan-Hu-1 was obtained from Nigel Temperton, University of Kent. The S gene of B.1.351 (South Africa) was based on the codon-optimised sequence of the Wuhan-Hu-1 expression construct, synthesised by Genscript (Netherlands) and sub-cloned into the pCDNA6 expression vector. S gene constructs bearing the B.1.617.1 and B.1.617.2 S genes were based on the codon-optimised spike sequence of SARS-CoV-2 ²⁰ and generated using the QuikChange Multi Site-Directed Mutagenesis Kit (Agilent, USA).

Constructs bore the following mutations relative to the Wuhan-Hu-1 sequence (GenBank: MN908947 ) B.1.351 – D80A, D215G, L241-243del, K417N, E484K, N501Y, D614G, A701V; B.1.617.1 – T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H; B.1.617.2 – T19R, G142D, E156del, F157del, R158G, L452R, T478K, D614G, P681R, D950N. 293-ACE2 target cells ¹⁷ were maintained in complete DMEM supplemented with 2µg/ml puromycin.

Neutralising activity in each sample was measured by a serial dilution approach. Each sample was serially diluted in triplicate from 1:50 to 1:36450 in complete DMEM prior to incubation with HIV (SARS-CoV-2) pseudotypes, incubated for 1 hour, and plated onto 239-ACE2 target cells.

After 48-72 hours, luciferase activity was quantified by the addition of Steadylite Plus chemiluminescence substrate and analysis on a Perkin Elmer EnSight multimode plate reader (Perkin Elmer, Beaconsfield, UK). Antibody titre was then estimated by interpolating the point at which infectivity had been reduced to 90% of the value for the no serum control samples.

 

I know this is a heavy duty slog, but this paper really gets to meat of what I have been saying for months and is from the UK, thus it is germane to many on here.

Edited July 5, 2021 by Vesper

[Tomo 21,681]

2 hours ago, Jas said:

Wahey. FINALLY got my first jab but now have to deal with a sore arm for a few days. lol

I didn't even get that.

Although from what I'm hearing i won't be as lucky next time round.

[Jase 43,479]

2 hours ago, Tomo said:

I didn't even get that.

Although from what I'm hearing i won't be as lucky next time round.

TBF, the side effect(s) can vary from one person to another and it's more intense it seems once you get the second jab. 

Which vaccine did you get, if I may ask? I got the Pfizer one.

[Tomo 21,681]

6 minutes ago, Jas said:

TBF, the side effect(s) can vary from one person to another and it's more intense it seems once you get the second jab. 

Which vaccine did you get, if I may ask? I got the Pfizer one.

Pfizer, felt a bit strange in the 15 minute waiting area but beyond that it felt like I didn't have it. Was quite good timing actually as I've gone to work in Scotland for a few weeks and cases are going through the roof here.

Edited July 5, 2021 by Tomo

[Jase 43,479]

9 minutes ago, Tomo said:

Pfizer, felt a bit strange in the 15 minute waiting area but beyond that it felt like I didn't have it. Was quite good timing actually as I've gone to work in Scotland for a few weeks and cases are going through the roof here.

I just can't wait to get the second dose so that I don't have to feel overly paranoid when wanting to head out. 

[Laylabelle 9,300]

And Boris has listed everything..see how this goes. Hopefully works out well! Esp if hospital cases are low

[NikkiCFC 7,589]

I am going to festival later this week with 50k people there per night. A lot of us are not vaccinated but they provide free rapid antigen test so let's see how that goes... A lot of Brits will also come as usual so I expect this Delta variant to blow here as well after. 

[Vesper 27,337]

I Misjudged The Pandemic In 2020. We're Making The Same Mistake in 2021.

The Delta variant of the SARS-CoV-2 virus that began in India is currently blitzkrieging its way around the globe. It is time to take it very, very seriously.

https://thebanter.substack.com/p/i-misjudged-the-pandemic-in-2020

by Bob Cesca

WASHINGTON, DC -- Back in February 2020, I misjudged the pandemic. 

At the time, one of my podcast co-hosts, David “TRex” Ferguson, mentioned to me that we ought to be talking more about “this coronavirus thing” that was popping up in the news with increasingly urgent frequency. Like many of us, I didn’t take it all that seriously at the time. I was focused on other issues and I didn’t feel as though it was prevalent enough or threatening enough to warrant more than just a passing mention. I figured it’d come and go like the swine flu or the avian flu.

Boy, did I misjudge that one. 

It wasn’t until midway through March 2020 when I realized “this coronavirus thing” was going to be a serious global emergency. And how could it not have been? 

Donald Trump was calling the shots for the nation, so the old playbook for aggressively-yet-calmly handling an outbreak was going to be ignored. And it was. Trump’s response wasn’t really a response at all. His incompetence would boil to the surface in the face of the unthinkable: a crisis that would expose a completely unprepared and grotesquely maladroit chief executive, proving he had no business visiting the White House as a tourist much less presiding as the shrieking a-hole behind the Resolute Desk. 

Trump’s incompetence, however, was amplified by his deliberate ignorance and singular focus on getting re-elected that November -- at any cost. It turned out, hundreds of thousands of dead Americans would be the price tag for Trump’s vast dumbness and malignant narcissism. He sacrificed all those people, on top of the rest of us who sacrificed a year of our lives by isolating in place, by urging Americans to ignore responsible protocols -- framing himself as a lockdown Santa Claus -- the good cop to science’s bad cop. Trump figured if he pandered to and indulged Americans, they’d reward him by keeping the economy afloat and re-electing him in November.

By Election Day 2020, 231,353 Americans were dead -- prior to the massive Winter surge -- due in large part to Trump’s monstrous political and financial ambitions. 

And he didn’t even win. He gambled with all those lives and lost anyway.

Fast forward to this week and we’re seeing echoes of those early days of the COVID-19 pandemic in the form of news about the Delta variant of the SARS-CoV-2 virus that began in India and is currently blitzkrieging its way around the globe.

I don’t intend to make the same error in judgment on this one, I assure you. Why?

• In the United Kingdom, 97 percent of the cases by mid-June were caused by the Delta variant. 

• According to the Wall Street Journal, “Almost half of the [UK’s] recent Covid-19 deaths are of people who have been vaccinated.”

• The Delta variant, along with unvaccinated Americans, created a nine percent uptick in new cases nationwide.

• 80 percent of new cases in four states, Missouri, Connecticut, Kansas, and Arkansas, are reportedly due to the Delta variant. 96 percent of Missouri’s cases are Delta.

• Israel’s Health Ministry released a data dump this week with some startling numbers. The Pfizer-BioNTech vaccine’s efficacy against Delta seems to have dropped from 94 percent to 64 percent, and the infection appears to be somewhat spreadable to people with two Pfizer vaccinations given the fact that, similar to the UK, Israel reported that half of its COVID cases -- as opposed to COVID deaths -- are among vaccinated people.

• And finally, Japan has declared another state of emergency for Tokyo ahead of the Summer Olympics this month, due to the Delta variant. This means it’s unlikely there will be live audiences for the events. More importantly, the emergency should serve as a wake-up call: COVID isn’t done with us yet.

All told, the Delta variant is gaining steam with similar velocity as the earliest days of the original pandemic, and we should probably keep a closer eye on the rise of this new strain, including being extra careful to distance from if not outright avoid unvaccinated people whenever possible. And by the way, Tucker Carlson, with his anti-vax pandering, can feel free to suck it.

Now the good news: with a new and infinitely more competent president in running things this year, I’m confident that far better decisions will be made as we awaken to this new Delta threat. That said, the White House isn’t the only entity that needs to do better if and when this next thing lands in our laps. Even though vaccinated people are reportedly testing positive, vaccinations are still our best chance at beating the virus and its offspring. As the situation gets increasingly confusing with variants and questions about who can infect whom, the great equalizer is getting vaccinated, while mustering the discipline to distance from the unvaxxed whenever possible. If we’re all vaccinated, there’s no more guesswork, and with that, peace of mind -- or as close to peace of mind we can attain these days.

A former president once said, “Fool me once, shame on you. Fool me -- y’can’t get fooled again.” 

Unlike those early, early, early days, I’m awake and paying attention now. 

[Vesper 27,337]

[Vesper 27,337]

‘Living with the virus’ makes no sense. Only half of the UK is fully vaccinated

We’re heading towards 100,000 Covid cases a day, yet ministers laud ‘freedom day’. It seems no one is accountable

https://www.theguardian.com/commentisfree/2021/jul/07/living-with-the-virus-uk-vaccinated-covid-cases

After receiving my second vaccination in April, I contracted Covid a week ago. I’m now “living with the virus”, a phrase emblematic of the failure of UK public health. Just look at the relative death rates in China (population 1.4 billion), Vietnam (100 million), the United States (340 million) and the UK (68 million). When plotted on the same graph, you cannot see the death curves for those two Asian states because they are so low.

Britain’s leaders and their advisers told us last year that we could not suppress the virus. China and Vietnam did, within six weeks. They told us these countries would inevitably face a huge second wave. They haven’t; just smaller outbreaks, suppressed with good public health practice implemented by people on the ground.

As we know, exploding cases in March 2020 forced the UK into a 13-week full national lockdown, with huge damage to livelihoods, the economy and mental health. None of the east Asian states had national lockdowns, only local ones. In 2020, China’s GDP grew by 2% and Vietnam’s by 2.9%, according to the World Bank, compared with the UK’s 9.9% contraction.

Last summer the UK government set up a privatised, call centre-based test-and-trace system divorced from our underfunded local public health and primary care teams – quite unlike anything done in successful east Asian states. It couldn’t possibly work, and it didn’t. The Treasury refused to give any financial support to poorer people to isolate – in case, as the then health secretary, Matt Hancock, told a Commons select committee, they “gamed the system”. So poor families gamed the test-and-trace system instead, to keep working and feed their families. The virus simply spread, without public health control, and was only suppressed by two more prolonged national lockdowns.

The vaccines arrived with a huge wave of nationalistic fervour. We are world leaders, crowed the prime minister. The first to jab. Yes, our GP network stepped in magnificently to roll out the vaccines, but local authorities and public health remained deprived of any financial support. Meanwhile, test and trace staggered on, a fortune spent on private consultants, test companies and cronies. The £37bn spent was equivalent to a decade’s funding for the whole UK public health programme.

So the third lockdown now ends in a staggered and collapsing roadmap. In February the chief scientific adviser, Patrick Vallance, was alone among advisers saying that find, test, trace and isolate was crucial when case rates fell to low levels. On 19 May, we saw only 1,517 cases a day. Yet no changes were made to our ineffective test-and-trace system – it remained outsourced, with the lowest rate of financial compensation for isolation in any OECD country. So another wave began.

On Monday the prime minister told us we would have 50,000 cases a day by his so-called “freedom day” on 19 July. A day later the health secretary, Sajid Javid, said we could hit 100,000 a day this summer. But it was OK, he told us. We can “live with the virus” because we are all vaccinated.

Well, all except children, and the poorest and most hesitant groups. Actually, only half Britain’s population (34 million) is fully protected with vaccines. Yes, admissions and deaths will go up, but the government can’t say by how much. The possibility of the virus becoming vaccine-resistant was not mentioned. Vaccine protection appears much less effective at stopping infection than it does at preventing serious illness or death. Talk of long Covid is seemingly taboo among ministers, even though the latest government figures show more than 2 million people have lived with symptoms for at least 12 weeks. A new study has found measurable thinning of the brain cortex areas covering taste and smell in these patients.

And the government seems to think it fine for 8.8 million children up to age 16 to become infected – even though the US, Europe and Israel have vaccinated more than 7 million children because the benefits clearly outweigh the risks. Our vaccine committee is still thinking about it. Meanwhile, even in English school classrooms, masks are no longer required.

And what of the global vaccine shortage? At last month’s G7 meeting in Cornwall, President Joe Biden urged fellow leaders to share the patent with all countries so they can manufacture the vaccine themselves. The UK, Germany and Canada said no. Although 95% of funds to develop vaccines came from the public purse, it appears that the shareholders of big pharma companies must be protected. So a million people must die every month to sustain free markets.

New variants will emerge, but those same multinationals can make new vaccines – no doubt with new patents. No new G7 money was committed to the Covax global distribution scheme. And with Indian supplies blocked, Nepal, Bangladesh and the whole of Africa have virtually no vaccines.

Under the new libertarian public health system, “living with the virus” means we must not compromise people’s freedom to do what they like. If you prefer to cough and sneeze in a crowded commuter train, so be it: there’ll be no legal restriction on that. If porters, nurses, doctors, care workers, bus drivers or factory workers become infected, and if some of them die, so be it.

Seemingly no one is accountable. Politicians say they follow the science. Advisers say ministers must make the decisions. An explosion of cases is imminent, the burden on the NHS could be severe, and the threat of new variants that can break through the present vaccine protection is real, as I know. Rather than a merry-go-round of birthday honours and George Crosses, we need a plan to deal with the rampant third wave – one that will keep us safe.

[Vesper 27,337]

I cannot be more blunt.

That cunt BoJo and the fucking Tories, by going for a one jab only and then months wait for the 2nd vax (almost no other nation is doing that) has, is, and will kill thousands needlessly (especially as even though it prevents a majority of the chances of death and hospitalisation, you still get infected/spread the virus, so herd immunity is fucked up).

The Delta (and likely the new Lambda as well) variant simply runs roughshod over all the vaccines after one dose.  New studies are showing only a 10% efficacy rate. After 2 jabs the efficacy skyrockets. You do the maths.

Boris's head needs to be on a fucking pike, same as Trump's.

Dog help us all if Lambda is worse than Delta (and who knows what the next cooked-up variant will be like, Delta is now running riot in the US, and yet you still have 100 million cunts (the VAST majority MAGA Republicans) who are utterly refusing to vax and/or mask (and are violently resisting, including assaulting children who are masked).

Peru, where Lambda came from, is less than half the population of the UK, but now had 50% MORE deaths in toto now, its deaths per million is TRIPLE the UK rate now, after being 2 times lower than the UK before Lambda hit.

Quote

 

French researchers tested how well antibodies produced by natural infection and by coronavirus vaccines neutralize the Alpha, Beta and Delta variants, as well as a reference variant similar to the original version of the virus.

The researchers looked at blood samples from 103 people who had been infected with the coronavirus. Delta was much less sensitive than Alpha to samples from unvaccinated people in this group, the study found.

One dose of vaccine significantly boosted the sensitivity, suggesting that people who have recovered from Covid-19 still need to be vaccinated to fend off some variants.

The team also analyzed samples from 59 people after they had received the first and second doses of the AstraZeneca or Pfizer-BioNTech vaccines.

Blood samples from just 10 percent of people immunized with one dose of the AstraZeneca or the Pfizer-BioNTech vaccines were able to neutralize the Delta and Beta variants in laboratory experiments. But a second dose boosted that number to 95 percent. There was no major difference in the levels of antibodies elicited by the two vaccines.

“A single dose of Pfizer or AstraZeneca was either poorly or not at all efficient against Beta and Delta variants,” the researchers concluded.

 

 

[manpe 10,857]

@Vesper what are your thoughts on the Janssen vaccine? I'm thinking of getting that bc it's only one shot. 

[Vesper 27,337]

Lambda COVID variant: All you need to know about the new UK coronavirus strain

The new strain, previously referred as 'C.37' or the 'Andean' variant, has reached the UK. Here's what we know about the Lambda variant.

https://www.sciencefocus.com/news/lambda-variant/

 

Eight people have tested positive for the new Lambda variant of the coronavirus, which some have warned could be more transmissible than the Delta variant, which is currently the dominant strain in the UK.

A pre-print analysis, which has yet to be peer-reviewed, of the spike proteins on the SARS-CoV-2 Lambda variant showed a two-fold increase in infectivity, which scientists say is due to a particular mutation on the virus called the L452Q mutation.

The researchers at the NYU Grossman School of Medicine tested the effectiveness of mRNA vaccines – like the Pfizer and the Moderna coronavirus vaccines used in the UK – against the Lambda variant.

According to their results, there was a “partial resistance to neutralisation”, however this “is not likely to cause a significant loss of protection against infection” in vaccinated individuals.

The Lambda variant, also known as the C.37 strain, was first detected in Peru in August 2020, and it was classified as a variant of interest at the global level by the World Health Organization (WHO) on 15 June 2021.

This means the WHO consider it to have mutations with established, or suspected, implications for its transmissibility and severity, and has been detected in multiple countries.

Dr Maria Van Kerkhove, the WHO’s technical lead on COVID-19, said that they are tracking this strain to see if it should be classified as a variant of concern. This would happen if the strain “demonstrated properties of increased transmissibility,” or “if it has increased severity,” she said.

The Secretary of State for Health and Social Care, Sajid Javid, gave a statement to Parliament on 5 July that detailed the UK’s roadmap for easing restrictions.

“Of course the pandemic is not over,” said Javid. “The virus is still with us, it hasn’t gone away – and the risk of a dangerous new variant that evades vaccines remains real.

“We know that with COVID-19, the situation can change – and it can change quickly. But we cannot put our lives on hold forever.”

“There is currently limited evidence available about this variant,” Dr Alicia Demirjian, COVID Incident Director at Public Health England (PHE), told BBC Science Focus magazine.

“PHE, together with academic partners, is undertaking investigations to better understand the impact of the mutations on the behaviour of the virus. We are closely monitoring the situation in those countries where this variant is prevalent and where cases are detected in the UK, we are testing contacts and will undertake targeted case finding if required.”

How many cases of the Lambda variant have been detected in the UK?

As of 2 July 2021, there have been eight confirmed cases of the C.37 variant in the UK, all in England. The majority of these are linked to overseas travel, according to a PHE spokesperson.

Peru, where the strain was first detected, have reported that it is now the dominant variation, accounting for 71 per cent of all COVID-19 cases since January 2021.

A report by PHE on the variants of concern or under investigation in the UK shows that the Delta variant continues to be the prominent strain in the UK. In the week leading up to 30 June 2021, there were 50,824 new cases of the Delta variant, and a recent Government publication shows the Delta variant currently accounts for approximately 95 per cent of cases that are sequenced across the UK.

Will vaccines still work against the Lambda variant?

In a pre-print paper that has not yet been peer-reviewed, researchers found that mRNA vaccines are effective against the Lambda variant. Both the Pfizer and the Moderna coronavirus vaccines used in the UK are mRNA jabs, meaning they contain genetic material that instructs the body’s cells to produce coronavirus spikes, which then provokes an immune response.

The results of this paper suggest that vaccines in current use will remain protective against the Lambda variant.

However, in another pre-print paper, Lambda was found to have mutations that had “the ability to escape from neutralising antibodies elicited by CoronaVac“. CoronaVac is a vaccine being used in several Asian countries, and works by administering an inactive version of the SARS-CoV-2 virus, which then triggers an immune response.

Researchers have stressed that further studies are required to validate the effectiveness of vaccines.

Is the Lambda variant more transmissible?

While it is not known yet whether this new variant is more transmissible, scientists say the Lambda strain does carry a number of mutations that could potentially lead to increased transmissibility or increased resistance to the antibodies provided by a COVID-19 vaccination or prior exposure to the virus.

One of the mutations identified in the Lambda strain is referred to by scientists as T859N, and has been found in the so-called ‘Iota’ variant currently spreading in New York City.

Another mutation, at L452Q, is reported as being “similar to the mutation reported in the Delta and Epsilon variants” which is believed to affect its susceptibility to antibodies.

However, it’s important to note that research on this specific variant is all in early stages.

As there is currently little evidence to show exactly how the Lambda variant is different to the other strains, scientists say that further, more robust studies, are needed before we can understand the full extent of the strain’s effect.

What are the symptoms of the Lambda variant?

At present, there is nothing to suggest that the symptoms of infection with the new C.37, or Lambda, variant are different to other coronavirus strains.

The main symptoms of COVID-19, according to the NHS, are:

• a high temperature – this means you feel hot to touch on your chest or back (you do not need to measure your temperature)
• a new, continuous cough – this means coughing a lot for more than an hour, or three or more coughing episodes in 24 hours (if you usually have a cough, it may be worse than usual)
• a loss or change to your sense of smell or taste – this means you’ve noticed you cannot smell or taste anything, or things smell or taste different to normal

The NHS say that most people who have symptoms of COVID-19 will have at least one of the above.

What other variants of concern have been identified in the UK?

It is common for viruses to mutate when they replicate. Few of these small, genetic changes lead to a more harmful infection.

As of 2 July 2021, there are five strains considered to be ‘of concern’ by PHE, including the Delta and Alpha variants.

The UK Government has a deal with biopharmaceutical company CureVac to develop vaccines against future variants, and has pre-ordered 50 million doses.