Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant

Edara, Venkata Viswanadh; Floyd, Katharine; Lai, Lilin; Davis-Gardner, Meredith E.; Hudson, William Henry; Piantadosi, Anne; Waggoner, Jesse J.; Babiker, Ahmed; Ahmed, Rafi; Xie, Xuping; Lokugamage, Kumari G.; Menachery, Vineet D.; Shi, Pei–Yong; Suthar, Mehul S.

doi:10.1101/2021.02.02.21250799

Cited by 49 publications

(57 citation statements)

References 9 publications

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“…Studies addressing the effectiveness of the mRNA vaccines BNT162b2 (Pfizer–BioNTech; Mainz, Germany) and mRNA-1273 (Moderna; Cambridge, MA, USA) found that both infection-induced and vaccine-induced antibodies were effective in neutralising B.1.1.7. 34 , 35 , 36 The clinical efficacy of the ChAdOx1 vaccine (AstraZeneca; Cambridge, UK) against B.1.1.7 was found to be similar to the efficacy of the vaccine against other circulating lineages in the UK, according to a pre-print manuscript. 33 , 37 The ongoing clinical phase 3 trials of the protein-based vaccine NVX-CoV2373 (Novavax; Gaithersburg, MD, USA) reported 90% vaccine efficacy against the previous strains of SARS-CoV-2 and more than 85% efficacy against B.1.1.7.…”

Section: Discussionmentioning

confidence: 97%

Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study

Bager

Wohlfahrt

Fonager

et al. 2021

The Lancet Infectious Diseases

136

106

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Background The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. Methods We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. Findings Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72–0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25–1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period—the two covariates with the largest contribution to confounding of the crude RR. Interpretation Infection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7. Funding None.

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Section: Discussionmentioning

confidence: 97%

Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study

Bager

Wohlfahrt

Fonager

et al. 2021

The Lancet Infectious Diseases

136

106

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“…Within the the RBD, we and others have shown that the presence of N501Y mutation found in the B.1.1.7 UK variant does not affect the neutralizing ability of serum from either naturally infected or mRNA-1273 vaccinated individuals (Edara et al, 2021;Johnson et al, 2021;Rathnasinghe et al, 2021;Shen et al, 2021;Wu et al, 2021). The substitution at position E484, located in the receptor-binding ridge epitope (Greaney et al, 2021) (Johnson et al, 2021;Xie et al, 2021;Shen et al, 2021).…”

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confidence: 69%

Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant

Edara

Norwood

Floyd

et al. 2021

Cell Host & Microbe

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The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection-or vaccine-induced antibodies. We compared antibody binding and live virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.

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“…It is postulated to enhance transmissibility of the virus by facilitating a conformational change in the S protein following protease activity at the cell membrane [15]. Previous serum neutralization assays for VSV-based SARS-CoV-2 pseudoviruses expressing the S protein with the P681H mutation demonstrated no significant changes in the titer required for neutralization compared to the unmutated S protein [28]. Additionally, no significant changes in the titer were needed for neutralization of the WT SARS-CoV-2 compared to a viral sample from the B.1.1.7 variant (in which P681H is one of its defining mutations), using sera from convalescent patients or individuals vaccinated with the Moderna mRNA-1273 vaccine from Moderna [28].…”

Section: Discussionmentioning

confidence: 99%

A Unique SARS-CoV-2 Spike Protein P681H Variant Detected in Israel

et al. 2021

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The routine detection, surveillance, and reporting of novel SARS-CoV-2 variants is crucial, as these threaten to hinder global vaccination efforts. Herein we report a novel local variant with a non-synonymous mutation in the spike (S) protein P681H. This local Israeli variant was not associated with a higher infection rate or higher prevalence. Furthermore, the local variant was successfully neutralized by sera from fully vaccinated individuals at a comparable level to the B.1.1.7 variant and an Israel wild-type strain. While it is not a variant of concern, routine monitoring by sequencing is still required.

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Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant

Cited by 49 publications

References 9 publications

Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study

Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study

Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant

A Unique SARS-CoV-2 Spike Protein P681H Variant Detected in Israel

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