COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection

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Abstract

Coronavirus Disease 2019 (COVID-19) has been the most severe public health challenge in this century. Two years after its emergence, the rapid development and deployment of effective COVID-19 vaccines have successfully controlled this pandemic and greatly reduced the risk of severe illness and death associated with COVID-19. However, due to its ability to rapidly evolve, the SARS-CoV-2 virus may never be eradicated, and there are many important new topics to work on if we need to live with this virus for a long time. To this end, we hope to provide essential knowledge for researchers who work on the improvement of future COVID-19 vaccines. In this review, we provided an up-to-date summary for current COVID-19 vaccines, discussed the biological basis and clinical impact of SARS-CoV-2 variants and subvariants, and analyzed the effectiveness of various vaccine booster regimens against different SARS-CoV-2 strains. Additionally, we reviewed potential mechanisms of vaccine-induced severe adverse events, summarized current studies regarding immune correlates of protection, and finally, discussed the development of next-generation vaccines.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12929-022-00853-8.

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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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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett … (2020)

Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260

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Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

B Korber, W.M. Fischer, S. Gnanakaran … (2020)

Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

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Author and article information

Contributors

T.-C. Wu:

ORCID: http://orcid.org/0000-0003-1623-4584

wutc@jhmi.edu

Journal

Journal ID (nlm-ta): J Biomed Sci

Journal ID (iso-abbrev): J Biomed Sci

Title: Journal of Biomedical Science

Publisher: BioMed Central (London )

ISSN (Print): 1021-7770

ISSN (Electronic): 1423-0127

Publication date (Electronic): 15 October 2022

Publication date PMC-release: 15 October 2022

Publication date Collection: 2022

Volume: 29

Electronic Location Identifier: 82

Affiliations

[1 ]GRID grid.5386.8, ISNI 000000041936877X, Physiology, Biophysics and Systems Biology Graduate Program, , Weill Cornell Medicine, ; New York, NY USA

[2 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Molecular and Cellular Biology, , Harvard University, ; Cambridge, MA USA

[3 ]GRID grid.51462.34, ISNI 0000 0001 2171 9952, Tri-Institutional PhD Program in Chemical Biology, , Memorial Sloan Kettering Cancer Center, ; New York, NY USA

[4 ]GRID grid.429509.3, ISNI 0000 0004 0491 4256, International Max Planck Research School for Immunobiology, Epigenetics and Metabolism (IMPRS-IEM), Max Planck Institute of Immunobiology and Epigenetics, ; Freiburg, Germany

[5 ]GRID grid.5963.9, Department of Urology, Medical Center, , University of Freiburg, ; Freiburg, Germany

[6 ]GRID grid.5963.9, Faculty of Biology, , University of Freiburg, ; Freiburg, Germany

[7 ]Downstream Process Science, EirGenix Inc., Zhubei, Hsinchu, Taiwan R.O.C.

[8 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Pathology, , Johns Hopkins University, ; Baltimore, MD USA

[9 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Oncology, , Johns Hopkins University, ; Baltimore, MD USA

[10 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Obstetrics and Gynecology, , Johns Hopkins University, ; Baltimore, MD USA

[11 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Microbiology and Immunology, , Johns Hopkins University, ; Baltimore, MD USA

[12 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, The Johns Hopkins Medical Institutions, ; CRB II Room 309, 1550 Orleans St, MD 21231 Baltimore, USA

Author information

T.-C. Wu http://orcid.org/0000-0003-1623-4584

Article

Publisher ID: 853

DOI: 10.1186/s12929-022-00853-8

PMC ID: 9569411

PubMed ID: 36243868

SO-VID: 249b1e65-631e-4d9c-ab83-945ff40b6f8e

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Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 May 2022

Date accepted : 1 September 2022

Funding

Funded by: NIH National Cancer Institute

Award ID: P50 CA098252

Award Recipient : T.-C. Wu

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ScienceOpen disciplines: Molecular medicine

Keywords: covid-19,vaccine,immunity,variant,sars-cov-2

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ScienceOpen disciplines: Molecular medicine

Keywords: covid-19, vaccine, immunity, variant, sars-cov-2

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COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection

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Novel Coronavirus Disease COVID-19

Most cited references 249

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

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Cited by 40

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