Abstract
As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also prevent transmission are needed to help reduce global disease burden. Currently approved parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here we describe the development of a novel vaccine strategy, Prime and Spike, based on unadjuvanted intranasal spike boosting that leverages existing immunity generated by primary vaccination to elicit mucosal immune memory within the respiratory tract. We show that Prime and Spike induces robust T resident memory cells, B resident memory cells and IgA 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 induction of cross-reactive immunity against sarbecoviruses without invoking original antigenic sin.
One-sentence summary Broad sarbecovirus protective mucosal immunity is generated by unadjuvanted intranasal spike boost in preclinical model.
Competing Interest Statement
W.M.S. and A.I. are cofounders of Xanadu Bio. A.I., B.I., and T.M. are listed as inventors on patent applications relating to intranasal spike-based SARS-CoV-2 vaccines filed by the Yale University. A.I., W.M.S., B.I., T.M, A.S., and M.H. are listed as inventors on patent applications relating to intranasal PACE nanoparticle delivery-based vaccines filed by Yale University.
