Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters

• Published in: PLoS pathogens Vol. 19; no. 6; p. e1011057
• Main Authors: Liu, Xueqiao, Park, Hong-Su, Matsuoka, Yumiko, Santos, Celia, Yang, Lijuan, Luongo, Cindy, Moore, Ian N., Johnson, Reed F., Garza, Nicole L., Zhang, Peng, Lusso, Paolo, Best, Sonja M., Buchholz, Ursula J., Le Nouën, Cyril
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2023; Public Library of Science (PLoS)
• Subjects: Age groups; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antibody response; Antigens; Biology and life sciences; Cattle; Child; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; Cricetinae; Diseases; Dosage and administration; Genes; Growth; Hamsters; Humans; Immunization; Immunogenicity; Immunoglobulin A; Immunoglobulin G; Infections; Influenza vaccines; Medicine and health sciences; Parainfluenza; Parainfluenza Virus 3, Human; Paramyxoviridae Infections; Pathogens; Pediatrics; Prevention; Proteins; Respiratory syncytial virus; Risk factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Sucrose; Vaccines; Vaccines, Attenuated; Viral Fusion Proteins; Virus diseases; Viruses; Weight loss; Syria
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011057

The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2.