Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

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Abstract

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.

Abstract

At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Matplotlib: A 2D Graphics Environment

John Hunter (2007)

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Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

S Altschul (1997)

The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

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Author and article information

Contributors

Shay Ben-Shachar:

ORCID: http://orcid.org/0000-0001-7994-5805

shayb@clalit.org.il

Adi Stern:

ORCID: http://orcid.org/0000-0002-2919-3542

sternadi@tauex.tau.ac.il

Journal

Journal ID (nlm-ta): Nat Med

Journal ID (iso-abbrev): Nat Med

Title: Nature Medicine

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date (Electronic): 14 June 2021

Publication date PMC-release: 14 June 2021

Publication date (Print): 2021

Volume: 27

Issue: 8

Pages: 1379-1384

Affiliations

[1 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, , Tel Aviv University, ; Tel Aviv, Israel

[2 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, Edmond J. Safra Center for Bioinformatics, , Tel Aviv University, ; Tel Aviv, Israel

[3 ]GRID grid.414553.2, ISNI 0000 0004 0575 3597, Clalit Research Institute, Innovation Division, , Clalit Health Services, ; Ramat Gan, Israel

[4 ]GRID grid.414553.2, ISNI 0000 0004 0575 3597, Clalit Health Services, Central Laboratories, , Haifa and Western Galilee, ; Nesher, Israel

[5 ]GRID grid.414553.2, ISNI 0000 0004 0575 3597, Progenin Laboratories, Jerusalem District, , Clalit Health Services, ; Tel Aviv, Israel

[6 ]GRID grid.413156.4, ISNI 0000 0004 0575 344X, Microbiology lab, Rabin Medical Center, , Beilinson Hospital, ; Petah Tiqva, Israel

[7 ]GRID grid.414553.2, ISNI 0000 0004 0575 3597, Central Laboratory, , Clalit Health Services, ; Tel Aviv, Israel

[8 ]GRID grid.7489.2, ISNI 0000 0004 1937 0511, Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, , Ben Gurion University of the Negev, ; Beersheba, Israel

[9 ]GRID grid.469889.2, ISNI 0000 0004 0497 6510, Microbiology Laboratory, , Emek Medical Center, ; Afula, Israel

[10 ]GRID grid.412686.f, ISNI 0000 0004 0470 8989, Laboratory of Clinical Virology, , Soroka University Medical Center, ; Beersheba, Israel

[11 ]GRID grid.7489.2, ISNI 0000 0004 1937 0511, Faculty of Health Sciences, , Ben Gurion University of the Negev, ; Beersheba, Israel

[12 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, The Bio-statistical and Bio-mathematical Unit, The Gertner Institute for Epidemiology and Health Policy Research, , Chaim Sheba Medical Center, Tel HaShomer, ; Ramat Gan, Israel

[13 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, The Sackler Faculty of Medicine, , Tel-Aviv University, ; Tel Aviv, Israel

[14 ]GRID grid.414553.2, ISNI 0000 0004 0575 3597, Clalit Health Services, ; Tel Aviv, Israel

Author information

Talia Kustin http://orcid.org/0000-0001-5677-4150

Shay Ben-Shachar http://orcid.org/0000-0001-7994-5805

Adi Stern http://orcid.org/0000-0002-2919-3542

Article

Publisher ID: 1413

DOI: 10.1038/s41591-021-01413-7

PMC ID: 8363499

PubMed ID: 34127854

SO-VID: 62787159-82cd-4303-8603-e10cc9e0cec6

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 30 April 2021

Date accepted : 26 May 2021

Funding

Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);

Award ID: 852223

Award Recipient : Adi Stern

Funded by: sraeli Science Foundation grant 3963/19

Funded by: Edmond J. Safra Center for Bioinformatics at Tel-Aviv University

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ScienceOpen disciplines: Medicine

Keywords: sars-cov-2,phylogenetics,viral infection

Data availability:

ScienceOpen disciplines: Medicine

Keywords: sars-cov-2, phylogenetics, viral infection

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Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

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Novel Coronavirus Disease COVID-19

Most cited references 36

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Matplotlib: A 2D Graphics Environment

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

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Cited by 163

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