An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Ahmed O. Hassan; Swathi Shrihari; Matthew J. Gorman; Baoling Ying; Dansu Yaun; Saravanan Raju; Rita E. Chen; Igor P. Dmitriev; Elena Kashentseva; Lucas J. Adams; Colin Mann; Meredith E. Davis-Gardner; Mehul S. Suthar; Pei Yong Shi; Erica Ollmann Saphire; Daved H. Fremont; David T. Curiel; Galit Alter; Michael S. Diamond

doi:10.1016/j.celrep.2021.109452

An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Ahmed O. Hassan, Swathi Shrihari, Matthew J. Gorman, Baoling Ying, Dansu Yaun, Saravanan Raju, Rita E. Chen, Igor P. Dmitriev, Elena Kashentseva, Lucas J. Adams, Colin Mann, Meredith E. Davis-Gardner, Mehul S. Suthar, Pei Yong Shi, Erica Ollmann Saphire, Daved H. Fremont, David T. Curiel, Galit Alter, Michael S. Diamond

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

Abstract

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

Original language	English
Article number	109452
Journal	Cell Reports
Volume	36
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2021.109452
State	Published - Jul 27 2021

Keywords

COVID-19
SARS-CoV-2
antibody
durability
mice
mucosal immunity
pathogenesis
vaccine
variants of concern

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10.1016/j.celrep.2021.109452

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Hassan, A. O., Shrihari, S., Gorman, M. J., Ying, B., Yaun, D., Raju, S., Chen, R. E., Dmitriev, I. P., Kashentseva, E., Adams, L. J., Mann, C., Davis-Gardner, M. E., Suthar, M. S., Shi, P. Y., Saphire, E. O., Fremont, D. H., Curiel, D. T., Alter, G., & Diamond, M. S. (2021). An intranasal vaccine durably protects against SARS-CoV-2 variants in mice. Cell Reports, 36(4), Article 109452. https://doi.org/10.1016/j.celrep.2021.109452

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title = "An intranasal vaccine durably protects against SARS-CoV-2 variants in mice",

abstract = "SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.",

keywords = "COVID-19, SARS-CoV-2, antibody, durability, mice, mucosal immunity, pathogenesis, vaccine, variants of concern",

author = "Hassan, {Ahmed O.} and Swathi Shrihari and Gorman, {Matthew J.} and Baoling Ying and Dansu Yaun and Saravanan Raju and Chen, {Rita E.} and Dmitriev, {Igor P.} and Elena Kashentseva and Adams, {Lucas J.} and Colin Mann and Davis-Gardner, {Meredith E.} and Suthar, {Mehul S.} and Shi, {Pei Yong} and Saphire, {Erica Ollmann} and Fremont, {Daved H.} and Curiel, {David T.} and Galit Alter and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

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day = "27",

doi = "10.1016/j.celrep.2021.109452",

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Hassan, AO, Shrihari, S, Gorman, MJ, Ying, B, Yaun, D, Raju, S, Chen, RE, Dmitriev, IP, Kashentseva, E, Adams, LJ, Mann, C, Davis-Gardner, ME, Suthar, MS, Shi, PY, Saphire, EO, Fremont, DH , Curiel, DT, Alter, G & Diamond, MS 2021, 'An intranasal vaccine durably protects against SARS-CoV-2 variants in mice', Cell Reports, vol. 36, no. 4, 109452. https://doi.org/10.1016/j.celrep.2021.109452

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AU - Hassan, Ahmed O.

AU - Shrihari, Swathi

AU - Gorman, Matthew J.

AU - Ying, Baoling

AU - Yaun, Dansu

AU - Raju, Saravanan

AU - Chen, Rita E.

AU - Dmitriev, Igor P.

AU - Kashentseva, Elena

AU - Adams, Lucas J.

AU - Mann, Colin

AU - Davis-Gardner, Meredith E.

AU - Suthar, Mehul S.

AU - Shi, Pei Yong

AU - Saphire, Erica Ollmann

AU - Fremont, Daved H.

AU - Curiel, David T.

AU - Alter, Galit

AU - Diamond, Michael S.

PY - 2021/7/27

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N2 - SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

AB - SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

KW - COVID-19

KW - SARS-CoV-2

KW - antibody

KW - durability

KW - mice

KW - mucosal immunity

KW - pathogenesis

KW - vaccine

KW - variants of concern

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DO - 10.1016/j.celrep.2021.109452

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JO - Cell Reports

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ER -

An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

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Keywords

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