Mutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine.
attenuated
cold-adapted
ferrets
guinea pigs
influenza A virus
live-attenuated influenza vaccines
master donor virus
protection efficacy
temperature sensitive
transmission
vaccines
Journal
Microbiology spectrum
ISSN: 2165-0497
Titre abrégé: Microbiol Spectr
Pays: United States
ID NLM: 101634614
Informations de publication
Date de publication:
29 06 2022
29 06 2022
Historique:
pubmed:
19
5
2022
medline:
2
7
2022
entrez:
18
5
2022
Statut:
ppublish
Résumé
Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the
Identifiants
pubmed: 35583364
doi: 10.1128/spectrum.00078-22
pmc: PMC9241597
doi:
Substances chimiques
Influenza Vaccines
0
Vaccines, Attenuated
0
Viral Proteins
0
influenza virus polymerase basic protein 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007822Subventions
Organisme : NICHD NIH HHS
ID : K12 HD000850
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145332
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI118689
Pays : United States
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