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Open accessJournal ArticleDOI: 10.1136/BMJ.N597

Covid-19: Where are we on vaccines and variants?

02 Mar 2021-BMJ (British Medical Journal Publishing Group)-Vol. 372
Abstract: Nearly a year after WHO declared the covid-19 pandemic, Elisabeth Mahase reports on the latest developments in vaccines, variants, and diplomacy

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Open accessJournal ArticleDOI: 10.1038/S41579-021-00573-0
Abstract: Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

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Topics: Mutation (52%), Population (52%), Viral evolution (51%) ... show more

334 Citations


Open accessPosted ContentDOI: 10.1101/2021.06.23.21259327
Chris Davis1, Nicola S Logan1, Grace Tyson1, Richard J. Orton1  +12 moreInstitutions (3)
28 Jun 2021-medRxiv
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.

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Topics: Vaccine efficacy (58%), Vaccination (57%), Antigenic drift (53%)

21 Citations


Open accessJournal ArticleDOI: 10.1371/JOURNAL.PCBI.1009288
Abstract: Mass vaccination offers a promising exit strategy for the COVID-19 pandemic. However, as vaccination progresses, demands to lift restrictions increase, despite most of the population remaining susceptible. Using our age-stratified SEIRD-ICU compartmental model and curated epidemiological and vaccination data, we quantified the rate (relative to vaccination progress) at which countries can lift non-pharmaceutical interventions without overwhelming their healthcare systems. We analyzed scenarios ranging from immediately lifting restrictions (accepting high mortality and morbidity) to reducing case numbers to a level where test-trace-and-isolate (TTI) programs efficiently compensate for local spreading events. In general, the age-dependent vaccination roll-out implies a transient decrease of more than ten years in the average age of ICU patients and deceased. The pace of vaccination determines the speed of lifting restrictions; Taking the European Union (EU) as an example case, all considered scenarios allow for steadily increasing contacts starting in May 2021 and relaxing most restrictions by autumn 2021. Throughout summer 2021, only mild contact restrictions will remain necessary. However, only high vaccine uptake can prevent further severe waves. Across EU countries, seroprevalence impacts the long-term success of vaccination campaigns more strongly than age demographics. In addition, we highlight the need for preventive measures to reduce contagion in school settings throughout the year 2021, where children might be drivers of contagion because of them remaining susceptible. Strategies that maintain low case numbers, instead of high ones, reduce infections and deaths by factors of eleven and five, respectively. In general, policies with low case numbers significantly benefit from vaccination, as the overall reduction in susceptibility will further diminish viral spread. Keeping case numbers low is the safest long-term strategy because it considerably reduces mortality and morbidity and offers better preparedness against emerging escape or more contagious virus variants while still allowing for higher contact numbers (freedom) with progressing vaccinations.

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Topics: European union (54%), Population (51%)

16 Citations


Open accessPosted ContentDOI: 10.1101/2021.05.20.21257461
Julia Shapiro1, Natalie E. Dean1, Zachary J. Madewell1, Yang Yang1  +3 moreInstitutions (3)
21 May 2021-medRxiv
Abstract: In this report, we provide summary estimates, from publications and reports, of vaccine efficacy (VE) for the COVID-19 vaccines that are being rolled out on a global scale. We find that, on average, the efficacy against any disease with infection is 85% (95% CI: 71 - 93%) after a fully course of vaccination. The VE against severe disease, hospitalization or death averages close to 100%. The average VE against infection, regardless of symptoms, is 84% (95% CI: 70 - 91%). We also find that the average VE against transmission to others for infected vaccinated people is 54% (95% CI: 38 - 66%). Finally, we prove summary estimates of the VE against any disease with infection for some of the variants of concern (VOC). The average VE for the VOC B.1.1.7, B.1.1.28 (P1) and B.1.351 are 86% (95% CI: 65 - 84%), 61% (95% CI: 43 - 73%) and 56% (95% CI: 29 - 73%), respectively.

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13 Citations


Open accessJournal ArticleDOI: 10.3390/DIAGNOSTICS11060941
25 May 2021-
Abstract: Although universal vaccination is one of the most important healthcare strategies for limiting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) circulation and averting the huge number of hospitalizations and deaths due to coronavirus disease 2019 (COVID-19), significant inter-individual variability of COVID-19 vaccines’ efficacies has been described, mostly due to heterogeneous immune response in recipients. This opinion paper hence aims to discuss aspects related to the opportunity of monitoring anti-SARS-CoV-2 antibodies before and after COVID-19 vaccination, highlighting the pros and cons of this strategy. In summary, the advantages of anti-SARS-CoV-2 antibodies’ testing in recipients of COVID-19 vaccination encompass an assessment of baseline seroprevalence of SARS-CoV-2 infection in non-vaccinated individuals; early identification of low or non-responders to COVID-19 vaccination; and timely detection of faster decay of anti-SARS-CoV-2 antibody levels. In contrast, potential drawbacks to date include an unproven equivalence between anti-SARS-CoV-2 antibody titer, neutralizing activity, and vaccine efficiency; the lack of cost-effective analyses of different testing strategies; the enormous volume of blood drawings and increase of laboratory workload that would be needed to support universal anti-SARS-CoV-2 antibodies testing. A potential solution entails the identification of cohorts to be prioritized for testing, including those at higher risk of being infected by variants of concern, those at higher risk of unfavorable disease progression, and subjects in whom vaccine immunogenicity may be expectedly lower and/or shorter.

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Topics: Vaccination (56%)

11 Citations


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Open accessJournal ArticleDOI: 10.1016/S0140-6736(21)00234-8
20 Feb 2021-The Lancet
Abstract: Summary Background A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial at 25 hospitals and polyclinics in Moscow, Russia We included participants aged at least 18 years, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the 14 days before enrolment, and no other vaccinations in the 30 days before enrolment Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group Investigators, participants, and all study staff were masked to group assignment The vaccine was administered (0·5 mL/dose) intramuscularly in a prime-boost regimen: a 21-day interval between the first dose (rAd26) and the second dose (rAd5), both vectors carrying the gene for the full-length SARS-CoV-2 glycoprotein S The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose All analyses excluded participants with protocol violations: the primary outcome was assessed in participants who had received two doses of vaccine or placebo, serious adverse events were assessed in all participants who had received at least one dose at the time of database lock, and rare adverse events were assessed in all participants who had received two doses and for whom all available data were verified in the case report form at the time of database lock The trial is registered at ClinicalTrialsgov (NCT04530396) Findings Between Sept 7 and Nov 24, 2020, 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476) 19 866 received two doses of vaccine or placebo and were included in the primary outcome analysis From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14 964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6–95·2) Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events) 45 (0·3%) of 16 427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee Four deaths were reported during the study (three [ Interpretation This interim analysis of the phase 3 trial of Gam-COVID-Vac showed 91·6% efficacy against COVID-19 and was well tolerated in a large cohort Funding Moscow City Health Department, Russian Direct Investment Fund, and Sberbank

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Topics: Vaccine efficacy (61%), Interim analysis (54%), Case report form (52%) ... show more

549 Citations


Open accessJournal ArticleDOI: 10.1136/BMJ.N296
01 Feb 2021-BMJ
Abstract: The SARS-CoV-2 vaccine produced by the US biotechnology company Novavax is 956% effective against the original variant of SARS-CoV-2 but also provides protection against the newer variants B117 (856%) and B1351 (60%), preliminary data from clinical trials show Interim results have been released from a phase III trial carried out in the UK with more than 15 000 participants aged between 18 and 84, including 27% over the age of 65 The trial tested two doses of the vaccine administered three weeks apart and reported 62 symptomatic cases of covid-19, of which 56 were in the placebo group (saline) and six in the vaccine group Of the 62 cases, only one was severe (in the placebo group), and 32 were with the UK variant A phase II trial of the Novavax vaccine is also ongoing in South Africa with 4400 volunteers, in which …

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Topics: Vaccine efficacy (64%)

109 Citations


Open accessPosted ContentDOI: 10.1101/2021.02.23.21252259
Medini K. Annavajhala1, Hiroshi Mohri2, Pengfei Wang2, Manoj S. Nair2  +10 moreInstitutions (3)
25 Feb 2021-medRxiv
Abstract: Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here, we report the emergence of a novel variant lineage B.1.526 that contains E484K and its alarming rise to dominance in New York City in recent months. This variant is partially or completely resistant to two therapeutic monoclonal antibodies in clinical use. It is also less susceptible to neutralization by convalescent plasma or vaccinee sera, posing a modest antigenic challenge. The B.1.526 lineage has now been reported from all 50 states in the US and numerous other countries. B.1.526 has rapidly replaced non-variant lineages in New York, with an estimated transmission advantage of 35%. Although B.1.526 initially outpaced B.1.1.7 in the region, its growth has slowed concurrent with the rise of B.1.1.7. In states surrounding New York, B.1.526 continues to increase where B.1.1.7 has not yet reached dominance, persistently replacing non-variant lineages. Such transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, would warrant consideration of B.1.526 as a SARS-CoV-2 variant of concern.

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Topics: Lineage (genetic) (50%)

101 Citations


Open accessJournal ArticleDOI: 10.1136/BMJ.M4944
23 Dec 2020-BMJ
Abstract: The new SARS-CoV-2 variant has evoked scenes reminiscent of the early days of covid-19 when much of the world banned travel to and from Wuhan, China. With large parts of south-east England locked down, Elisabeth Mahase looks at what we know so far

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74 Citations


Open accessJournal ArticleDOI: 10.1136/BMJ.M4471
17 Nov 2020-BMJ
Abstract: The UK government has secured five million doses of the covid-19 vaccine candidate mRNA-1273 from US biotech company Moderna after interim analysis of its phase III trial showed it was 94.5% effective. If the vaccine meets standards of safety and effectiveness and is approved by the medicines regulator, the vaccine could be delivered to the UK and Europe as early as spring 2021 with the potential to procure more doses next year, a government statement said. The trial’s Data Safety Monitoring Board—which was appointed by the US National Institute of Health—carried out the analysis based on 95 covid-19 cases, of which 90 were observed in the placebo group and five were reported in the vaccine group. The trial enrolled more than 30 000 US participants, including 7000 aged over 65 and 5000 under 65 with high risk chronic diseases. More than one third (37%) of the trial …

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68 Citations


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