Q1 · BIOLOGY
Article
Author: Herbert, Richard ; Moore, Ian N ; Moore, Rashida ; Nelson, Christine E ; Johnson, Reed F ; Castens, Ashley ; Barber, Daniel L ; Le Nouën, Cyril ; Yang, Lijuan ; Lusso, Paolo ; Buchholz, Ursula J ; Liu, Xueqiao ; Santos, Celia ; Matsuoka, Yumiko ; Via, Laura E ; Zhang, Peng ; Park, Hong-Su ; Luongo, Cindy ; Garza, Nicole L ; Walker, April ; Munir, Shirin ; Wilder-Kofie, Temeri
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.