SUMMARY
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
One-Sentence Summary Intranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.
Competing Interest Statement
This research was supported by the Intramural Research Program of the NIAID, NIH (Project number ZIA AI001298-01). XL, CL, CLN, SM and UJB are inventors on the provisional patent application number 63/180,534, entitled: Recombinant chimeric bovine/human parainfluenza virus 3 expressing SARS-CoV-2 spike protein and its use, filed by the United States, Department of Health and Human Services.
