• Clin. Infect. Dis. · Aug 2021

    Absence of vaccine-enhanced disease with unexpected positive protection against SARS-CoV-2 by inactivated vaccine given within three days of virus challenge in Syrian hamster model.

    • Can Li, Yan-Xia Chen, Fei-Fei Liu, Andrew Chak-Yiu Lee, Yan Zhao, Zhan-Hong Ye, Jian-Piao Cai, Hin Chu, Rui-Qi Zhang, Kwok-Hung Chan, Kelvin Hei-Yeung Chiu, David Christopher Lung, Siddharth Sridhar, Ivan Fan-Ngai Hung, Kelvin Kai-Wang To, Anna Jin-Xia Zhang, Jasper Fuk-Woo Chan, and Kwok-Yung Yuen.
    • State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
    • Clin. Infect. Dis. 2021 Aug 2; 73 (3): e719-e734.

    BackgroundMass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described.MethodsTwo-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters.ResultsThe 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer.ConclusionsVaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

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