Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines

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Abstract

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first‐generation SARS‐CoV‐2 vaccines. Other sarbecoviruses, such as SARS‐CoV and SARS‐related coronaviruses (SARSr‐CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant‐proof SARS‐CoV‐2, pan‐sarbecovirus or pan‐β‐CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad‐spectrum neutralizing antibody responses and protective immunity to combat the current SARS‐CoV‐2 and its variants, other sarbecoviruses, as well as other β‐CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS‐CoV‐2 vaccines and summarized recent advances in broad‐spectrum vaccines against sarbecoviruses and β‐CoVs.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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A new coronavirus associated with human respiratory disease in China

Fan Wu, Su Zhao, Bin Yu … (2020)

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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Author and article information

Contributors

Qian Wang: wang_qian@fudan.edu.cn

Shibo Jiang:

ORCID: http://orcid.org/0000-0001-8283-7135

shibojiang@fudan.edu.cn

Journal

Journal ID (nlm-ta): J Med Virol

Journal ID (iso-abbrev): J Med Virol

Journal ID (doi): 10.1002/(ISSN)1096-9071

Journal ID (publisher-id): JMV

Title: Journal of Medical Virology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0146-6615

ISSN (Electronic): 1096-9071

Publication date (Electronic): 06 October 2022

Publication date PMC-release: 06 October 2022

Electronic Location Identifier: 10.1002/jmv.28172

Affiliations

[ ¹ ] Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences Fudan University Shanghai China

[ ² ] Department of Pharmacology, School of Pharmacy Fudan University Shanghai China

Author notes

[*] [* ] Correspondence Shibo Jiang and Qian Wang, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

Email: shibojiang@ 123456fudan.edu.cn and wang_qian@ 123456fudan.edu.cn

Author information

Lu Lu http://orcid.org/0000-0002-2255-0391

Shibo Jiang http://orcid.org/0000-0001-8283-7135

Article

Publisher ID: JMV28172

DOI: 10.1002/jmv.28172

PMC ID: 9538210

PubMed ID: 36161303

SO-VID: 52e56e8e-7733-45db-9e69-e0fda7b31370

License:

This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

History

Date revision received : 19 September 2022

Date received : 24 August 2022

Date accepted : 20 September 2022

Page count

Figures: 6, Tables: 3, Pages: 19, Words: 11024

Funding

Funded by: National Key Research and Development Program of China

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Funded by: Shanghai Municipal Science and Technology Major Project

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ScienceOpen disciplines: Microbiology & Virology

Keywords: covid‐19,pan‐sarbecovirus,pan‐β‐coronavirus,rbd,sars‐cov‐2,vaccines

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ScienceOpen disciplines: Microbiology & Virology

Keywords: covid‐19, pan‐sarbecovirus, pan‐β‐coronavirus, rbd, sars‐cov‐2, vaccines

Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines

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Novel Coronavirus Disease COVID-19

Most cited references 171

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

A new coronavirus associated with human respiratory disease in China

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

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