A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters.
Administration, Intranasal
Animals
Antibodies, Viral
/ blood
COVID-19
/ prevention & control
COVID-19 Vaccines
/ administration & dosage
Cricetinae
Genetic Vectors
Immunization
Parainfluenza Virus 3, Bovine
/ genetics
Parainfluenza Virus 3, Human
/ genetics
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ genetics
Vaccines, Attenuated
/ administration & dosage
Vaccines, Synthetic
/ administration & dosage
COVID-19
SARS-CoV-2
intranasal immunization
parainfluenza virus vaccines
vaccine vector
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 12 2021
14 12 2021
Historique:
accepted:
06
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
17
12
2021
Statut:
ppublish
Résumé
Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2-neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 10
Identifiants
pubmed: 34876520
pii: 2109744118
doi: 10.1073/pnas.2109744118
pmc: PMC8685679
pii:
doi:
Substances chimiques
Antibodies, Viral
0
COVID-19 Vaccines
0
Spike Glycoprotein, Coronavirus
0
Vaccines, Attenuated
0
Vaccines, Synthetic
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: X.L, C.L., C.L.N., S.M., and U.J.B. are inventors on the provisional patent application number 63/180,534, entitled “Recombinant chimeric bovine/human parainfluenza virus 3 expressing SARS-CoV-2 spike protein and its use,” filed by the United States, Department of Health and Human Services.
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