Cell · 2022
Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.
СтатьяНазвание и аннотация: Перевод в очереди
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Le Nouën Cyril, Nelson Christine E, Liu Xueqiao, Park Hong-Su, Matsuoka Yumiko, Luongo Cindy, Santos Celia, Yang Lijuan, Herbert Richard, Castens Ashley, Moore Ian N, Wilder-Kofie Temeri, Moore Rashida, Walker April, Zhang Peng, Lusso Paolo, Johnson Reed F, Garza Nicole L, Via Laura E, Munir Shirin, Barber Daniel L, Buchholz Ursula J
Аннотация
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 immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T cell responses, including tissue-resident memory cells in the 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.