Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a glycoprotein, expressed on the virion surface, that mediates infection of host cells by directly interacting with host receptors. As such, it is a reasonable target to neutralize the infectivity of the virus....

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Bibliographic Details
Published in:	Vaccine Vol. 41; no. 41; pp. 6025 - 6035
Main Authors:	Chiba, Shiho, Halfmann, Peter J., Iida, Shun, Hirata, Yuichiro, Sato, Yuko, Kuroda, Makoto, Armbrust, Tammy, Spyra, Samuel, Suzuki, Tadaki, Kawaoka, Yoshihiro
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 22-09-2023 Elsevier Limited
Subjects:	Adjuvants Amino acids Antibiotics Antibodies Antigens Binding Body weight Body weight loss Cloning Coronaviruses COVID-19 COVID-19 vaccines Glycoproteins Hamsters Immune response Immune system Immunity (Disease) Immunization Immunoglobulin G Infectivity Lungs Lymphocytes T mRNA vaccines Mutation Neutralizing Peptides Plasmids Proteins Receptors Recombinant protein vaccine Respiratory diseases Respiratory organs S protein SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Spike protein Splenocytes Syrian hamster Vaccines Variant viruses Viral diseases Virions Viruses Weight loss Weight reduction United States > US Japan Syrian hamster Adjuvants SARS-CoV-2 S protein Variant viruses Recombinant protein vaccine
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Summary:	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a glycoprotein, expressed on the virion surface, that mediates infection of host cells by directly interacting with host receptors. As such, it is a reasonable target to neutralize the infectivity of the virus. Here we found that a recombinant S protein vaccine adjuvanted with Alhydrogel or the QS-21-like adjuvant Quil-A effectively induced anti-S receptor binding domain (RBD) serum IgG and neutralizing antibody titers in the Syrian hamster model, resulting in significantly low SARS-CoV-2 replication in respiratory organs and reduced body weight loss upon virus challenge. Severe lung inflammation upon virus challenge was also strongly suppressed by vaccination. We also found that the S protein vaccine adjuvanted with Alhydrogel, Quil-A, or an AS03-like adjuvant elicited significantly higher neutralizing antibody titers in mice than did unadjuvanted vaccine. Although the neutralizing antibody titers against the variant viruses B.1.351 and B.1.617.2 declined markedly in mice immunized with wild-type S protein, the binding antibody levels against the variant S proteins were equivalent to those against wild-type S. When splenocytes from the immunized mice were re-stimulated with the S protein in vitro, the induced Th1 or Th2 cytokine levels were not significantly different upon re-stimulation with wild-type S or variant S, suggesting that the T-cell responses against the variants were the same as those against the wild-type virus. Upon Omicron XBB-challenge in hamsters, wild-type S-vaccination with Alhydrogel or AS03 reduced lung virus titers on Day 3, and the Quil-A adjuvanted group showed less body weight loss, although serum neutralizing antibody titers against XBB were barely detected in vitro. Collectively, recombinant vaccines coupled with different adjuvants may be promising modalities to combat new variant viruses by inducing various arms of the immune response.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0264-410X 1873-2518
DOI:	10.1016/j.vaccine.2023.08.054