A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2

Hassan, Ahmed O.; Kafai, Natasha M.; Dmitriev, Igor P.; Fox, Julie M.; Smith, Brittany K.; 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, Ya-Nan; Ma, Meisheng; Adams, Lucas J.; Shrihari, Swathi; Danis, Jonathan E.; Gralinski, Lisa E.; Hou, Yixuan J.; Schäfer, Alexandra; Kim, Arthur S.; Keeler, Shamus P.; Weiskopf, Daniela; Baric, Ralph S.; Holtzman, Michael J.; Fremont, Daved H.; Curiel, David T.; Diamond, Michael S.

Summary 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 neutralizing antibodies, promotes systemic and mucosal IgA and T cell responses, and virtually completely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.