Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques

Le Nouen, C.; Nelson, C. E.; Liu, X.; Park, H.-S.; Matsuoka, Y.; Luongo, C.; Santos, C.; Yang, L.; Herbert, R.; Castens, A.; Moore, I. N.; Wilder-Kofie, T.; Moore, R.; Walker, A.; Zhang, P.; Lusso, P.; Johnson, R. F.; Garza, N. L.; Via, L. E.; Munir, S.; Barber, D.; Buchholz, U. J.

doi:10.1101/2022.05.21.492923

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bioRxiv · 10.1101/2022.05.21.492923

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques

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Abstract

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 SummaryIntranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.

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Le Nouen, C., Nelson, C. E., Liu, X., Park, H.-S., Matsuoka, Y., Luongo, C., Santos, C., Yang, L., Herbert, R., Castens, A., Moore, I. N., Wilder-Kofie, T., Moore, R., Walker, A., Zhang, P., Lusso, P., Johnson, R. F., Garza, N. L., Via, L. E., Munir, S., Barber, D., Buchholz, U. J.. 2022-05-23. Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques. https://doi.org/10.1101/2022.05.21.492923

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