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

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 f...

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Bibliographic Details
Published in:PLoS pathogens 2023-06, Vol.19 (6), p.e1011057-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: Article
Language:English
Subjects:
Age groups
Antibodies
Antibody response
Antigens
Biology and life sciences
COVID-19 vaccines
Diseases
Dosage and administration
Genes
Growth
Hamsters
Immunization
Immunogenicity
Immunoglobulin A
Immunoglobulin G
Infections
Influenza vaccines
Medicine and health sciences
Parainfluenza
Pathogens
Pediatrics
Prevention
Proteins
Respiratory syncytial virus
Risk factors
Severe acute respiratory syndrome coronavirus 2
Spike protein
Sucrose
Vaccines
Virus diseases
Viruses
Weight loss
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011057