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

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

doi:10.1016/j.celrep.2021.109452

Abstract

SummarySARS-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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID19) syndrome, which can rapidly progress to pneumonia, respiratory failure, and systemic inflammatory disease (Cheung et al, 2020; Mao et al, 2020; Wichmann et al, 2020)
We recently described a single-dose, intranasally (IN)-delivered chimpanzee Adenovirus-based SARSCoV-2 vaccine (ChAd-SARS-CoV-2-S) encoding a pre-fusion stabilized S protein that induced robust humoral, cell-mediated, and mucosal immune responses and limited upper- and lowerairway infection in K18-hACE2 transgenic mice, hamsters, and non-human primates (Bricker et al, 2021; Hassan et al, 2020b, 2021)
A single ChAd-SARS-CoV-2-S immunization induces durable anti-spike and neutralizing responses at different doses We assessed the durability of humoral immune responses in BALB/c mice 100 or 200 days post-IM or IN immunization with escalating doses of ChAd-SARS-CoV-2-S (108, 109, and 1010 viral particles [vp]) or 1010 vp of a ChAd-Control vaccine (Figure 1A)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID19) syndrome, which can rapidly progress to pneumonia, respiratory failure, and systemic inflammatory disease (Cheung et al, 2020; Mao et al, 2020; Wichmann et al, 2020). The extensive morbidity and mortality associated with COVID-19 pandemic have made the development and deployment of SARS-CoV-2 vaccines an urgent global health priority. The spike (S) protein of the SARS-CoV-2 virion is the principal target for antibody-based and vaccine countermeasures. The S protein serves as the primary viral attachment and entry factor and engages the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) to promote SARS-CoV-2 entry into human cells (Letko et al, 2020). The prefusion form of the SARS-CoV-2 S protein (Wrapp et al, 2020) is recognized by potently neutralizing monoclonal antibodies (Barnes et al, 2020; Cao et al, 2020b; Pinto et al., Cell Reports 36, 109452, July 27, 2021 a 2021 The Author(s).

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