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 prefusion 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 immunoglobulin A (IgA) and T cell responses, and almost entirely 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. Graphical Abstract Highlights • Chimpanzee adenoviral vaccines encoding stabilized S induce neutralizing Abs • Chimpanzee adenoviral vaccines protect against SARS-CoV-2 infection and pneumonia • Intranasal vaccine delivery generates robust mucosal B and T cell responses • Intranasal ChAd-SARS-CoV-2 prevents upper and lower respiratory tract infection Intranasal or intramuscular immunization of ChAd-SARS-CoV-2, a chimpanzee adenoviral vaccine encoding stabilized spike protein, prevents SARS-CoV-2 lung infection and pneumonia in mice. In particular, intranasally delivered ChAd-SARS-CoV-2 uniquely prevents both upper and lower respiratory tract infections, potentially protecting against SARS-CoV-2 infection and transmission.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, Pathogenesis, antibody, T cells, protection, IgA, mucosal immunity, intranasal,