In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

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Abstract

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent history. In this review, we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus family. We will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2, MERS-CoV and the four seasonal coronaviruses (HCoV-OC43, NL63, HKU1 and 229E) in humans and the potential for future zoonotic coronaviruses. We will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine design. We will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer cross-protection. Finally, we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

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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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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

W. Joost Wiersinga, Andrew Rhodes, Allen Cheng … (2020)

The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.

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Contributors

L. Swadling:

ORCID: http://orcid.org/0000-0002-0537-6715

l.swadling@ucl.ac.uk

Journal

Journal ID (nlm-ta): Cell Mol Immunol

Journal ID (iso-abbrev): Cell Mol Immunol

Title: Cellular and Molecular Immunology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1672-7681

ISSN (Electronic): 2042-0226

Publication date (Electronic): 26 December 2023

Publication date PMC-release: 26 December 2023

Publication date (Print): February 2024

Volume: 21

Issue: 2

Pages: 103-118

Affiliations

Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, Pears Building, ( https://ror.org/02jx3x895) London, NW3 2PP UK

Author information

M. U. Demael http://orcid.org/0009-0001-0030-2469

L. Swadling http://orcid.org/0000-0002-0537-6715

Article

Publisher ID: 1116

DOI: 10.1038/s41423-023-01116-8

PMC ID: 10805787

PubMed ID: 38148330

SO-VID: f7f193f2-7db0-424f-98db-dcbf6a79c9f2

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 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/.

History

Date received : 1 November 2023

Date accepted : 21 November 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);

Award ID: MR/X502984/1

Award ID: MR/W006774/1

Award Recipient : M. U. Demael L. Swadling

Funded by: FundRef https://doi.org/10.13039/501100000268, RCUK | Biotechnology and Biological Sciences Research Council (BBSRC);

Award ID: BB/T008709/1

Award Recipient : S. Cankat

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ScienceOpen disciplines: Immunology

Keywords: vaccine,coronavirus,cross-reactive immunity,cross-protection,universal,vaccines,viral infection,cellular immunity,humoral immunity

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ScienceOpen disciplines: Immunology

Keywords: vaccine, coronavirus, cross-reactive immunity, cross-protection, universal, vaccines, viral infection, cellular immunity, humoral immunity

In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

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UCL: Covid-19 Research

Most cited references 166

A new coronavirus associated with human respiratory disease in China

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

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

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