Protection from COVID-19 Disease in Hamsters Vaccinated with Subunit SARS-CoV-2 S1 Mucosal Vaccines Adjuvanted with Different Adjuvants

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 6

PMID 37020550

Authors

Yongjun Sui

Hanne Andersen

Jianping Li

Tanya Hoang

Yonas Bekele

Swagata Kar

Mark G Lewis

Jay A Berzofsky

Affiliations

Soon will be listed here.

Abstract

Introduction: Adjuvant plays an important role in directing the immune responses induced by vaccines. In previous studies, we have shown that a mucosal SARS-CoV-2 S1 subunit vaccine adjuvanted with a combination of CpG, Poly I:C and IL-15 (named CP15) induced effective mucosal and systemic immunity and conferred nearly sterile protection against SARS-CoV-2 viral replication in macaque models.

Methods: In this study, we used a hamster model, which mimics the human scenario and reliably exhibits severe SARS-CoV-2 disease similar to hospitalized patients, to investigate the protection efficacy of the vaccines against COVID-19 disease. We compared the weight loss, viral loads (VLs), and clinical observation scores of three different vaccine regimens. All three regimens consisted of priming/boosting with S1 subunit vaccines, but adjuvanted with alum and/or CP15 administrated by either intramuscular (IM) or intranasal (IN) routes: Group 1 was adjuvanted with alum/alum administrated IM/IM; Group 2 was alum-IM/CP15-IN; and Group 3 was CP15-IM/CP15-IN.

Results: After challenge with SARS-CoV-2 WA strain, we found that the alum/CP15 group showed best protection against weight loss, while the CP15 group demonstrated best reduction of oral SARS-CoV-2 VLs, suggesting that the protection profiles were different. Sex differences for VL and clinical scores were observed. Humoral immunity was induced but not correlated with protection. Moreover, S1-specific binding antibody titers against beta, omicron BA.1, and BA.2 variants showed 2.6-, 4.9- and 2.8- fold reduction, respectively, compared to the Wuhan strain.

Discussion: Overall, the data suggested that adjuvants in subunit vaccines determine the protection profiles after SARS-CoV-2 infection and that nasal/oral mucosal immunization can protect against systemic COVID-19 disease.

Citing Articles

Adjuvanted subunit intranasal vaccine reduces SARS-CoV-2 onward transmission in hamsters.

Sui Y, Kar S, Chawla B, Hoang T, Yu Y, Wallace S Front Immunol. 2025; 16:1514845.

PMID: 39981227 PMC: 11841495. DOI: 10.3389/fimmu.2025.1514845.

Sex-biased immunogenicity of a mucosal subunit vaccine against SARS-CoV-2 in mice.

Li J, Hsu K, Howe S, Hoang T, Xia Z, Berzofsky J Front Immunol. 2024; 15:1386243.

PMID: 38835757 PMC: 11148259. DOI: 10.3389/fimmu.2024.1386243.

The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects.

Collins C, Longo D, Murphy W Front Immunol. 2024; 15:1345499.

PMID: 38469293 PMC: 10925677. DOI: 10.3389/fimmu.2024.1345499.

SARS-CoV-2 mucosal vaccine protects against clinical disease with sex bias in efficacy.

Sui Y, Andersen H, Li J, Hoang T, Minai M, Nagata B Vaccine. 2023; 42(2):339-351.

PMID: 38071106 PMC: 10843685. DOI: 10.1016/j.vaccine.2023.11.059.

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