A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

• Published in: Cell Vol. 183; no. 1; pp. 169 - 184.e13
• Main Authors: 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.
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 01.10.2020; Elsevier BV
• Subjects: Adenoviridae - genetics; Administration, Intranasal; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; antibody; Chlorocebus aethiops; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - prevention & control; COVID-19; COVID-19 Vaccines; Female; HEK293 Cells; Humans; IgA; Immunogenicity, Vaccine; Injections, Intramuscular; intranasal; Mice; Mice, Inbred BALB C; mucosal immunity; Pandemics; pathogenesis; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; protection; Respiratory Mucosa - immunology; Respiratory Mucosa - pathology; Respiratory Mucosa - virology; SARS-CoV-2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; T cells; vaccine; Vero Cells; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; COVID-19; pathogenesis; vaccine; SARS-CoV-2; IgA; antibody; intranasal; protection; T cells; mucosal immunity
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2020.08.026

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. [Display omitted] •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.