Prime-Pull Immunization of Mice with a BcfA-Adjuvanted Vaccine Elicits Sustained Mucosal Immunity That Prevents SARS-CoV-2 Infection and Pathology

Author:

Shamseldin Mohamed M.123ORCID,Kenney Adam1,Zani Ashley1,Evans John P.45ORCID,Zeng Cong45,Read Kaitlin A.1ORCID,Hall Jesse M.1,Chaiwatpongsakorn Supranee6ORCID,Mahesh K.C.6ORCID,Lu Mijia4ORCID,Eltobgy Mostafa1ORCID,Denz Parker1ORCID,Deora Rajendar12ORCID,Li Jianrong4,Peeples Mark E.67ORCID,Oestreich Kenneth J.1ORCID,Liu Shan-Lu1245ORCID,Corps Kara N.4,Yount Jacob S.1,Dubey Purnima1ORCID

Affiliation:

1. *Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH

2. †Department of Microbiology, The Ohio State University, Columbus, OH

3. ‡Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University−Ain Helwan, Helwan, Egypt

4. §Department of Veterinary Biosciences, The Ohio State University, Columbus, OH

5. ¶Center for Retrovirus Research, The Ohio State University, Columbus, OH

6. ‖Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH

7. #Department of Pediatrics, The Ohio State University, Columbus, OH

Abstract

Abstract Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy of Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in SARS-CoV-2 spike-based prime-pull immunizations. We show that i.m. priming of mice with an aluminum hydroxide– and BcfA-adjuvanted spike subunit vaccine, followed by a BcfA-adjuvanted mucosal booster, generated Th17-polarized CD4+ tissue-resident memory T cells and neutralizing Abs. Immunization with this heterologous vaccine prevented weight loss following challenge with mouse-adapted SARS-CoV-2 (MA10) and reduced viral replication in the respiratory tract. Histopathology showed a strong leukocyte and polymorphonuclear cell infiltrate without epithelial damage in mice immunized with BcfA-containing vaccines. Importantly, neutralizing Abs and tissue-resident memory T cells were maintained until 3 mo postbooster. Viral load in the nose of mice challenged with the MA10 virus at this time point was significantly reduced compared with naive challenged mice and mice immunized with an aluminum hydroxide–adjuvanted vaccine. We show that vaccines adjuvanted with alum and BcfA, delivered through a heterologous prime-pull regimen, provide sustained protection against SARS-CoV-2 infection.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

National Institutes of Health

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Cancer Institute

National Science Foundation

HHS | NIH | National Institute of General Medical Sciences

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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