A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Hassan, Ahmed O.; Kafai, Natasha M.; Dmitriev, Igor P.; Fox, Julie M.; Smith, Brittany; Harvey, Ian B.; Chen, Rita E.; Winkler, Emma S.; Wessel, Alex W.; Case, James Brett; Kashentseva, Elena; McCune, Broc T.; Bailey, Adam L.; Zhao, Haiyan; VanBlargan, Laura A.; Dai, Yanan; Ma, Meisheng; Adams, Lucas J.; Shrihari, Swathi; Gralinski, Lisa E.; Hou, Yixuan J.; Schaefer, Alexandra; Kim, Arthur S.; Keeler, Shamus P.; Weiskopf, Daniela; Baric, Ralph; Holtzman, Michael J.; Fremont, Daved H.; Curiel, David T.; Diamond, Michael S.

The Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.