Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses

View Publication on PubMed

Published

November 2022

Journal

Science

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa. We developed a vaccine strategy that we call "prime and spike," which leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract by using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, induces immunoglobulin A at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables the induction of cross-reactive immunity against sarbecoviruses.

Authors

Tianyang Mao, Benjamin Israelow, Mario A Peña-Hernández, Alexandra Suberi, Liqun Zhou, Sophia Luyten, Melanie Reschke, Huiping Dong, Robert J Homer, W Mark Saltzman, Akiko Iwasaki

Keywords

Animals; Mice; Administration, Intranasal; Antibodies, Viral; COVID-19/prevention & control/transmission; Immunity, Mucosal; SARS-CoV-2/immunology; Spike Glycoprotein, Coronavirus/immunology; Vaccination/methods; COVID-19 Vaccines/administration & dosage/immunology; Immunoglobulin A; Memory B Cells/immunology; Memory T Cells/immunology; Immunologic Memory