Details:

Alternative Title:
Infect Genet Evol
Personal Author:
Korenkov, Daniil A. ; Laurie, Karen L. ; Reading, Patrick C. ; Carolan, Louise A. ; Chan, Kok Fei ; ... More +
Korenkov, Daniil A. ; Laurie, Karen L. ; Reading, Patrick C. ; Carolan, Louise A. ; Chan, Kok Fei ; Isakova-Sivak, Irina I. ; Smolonogina, Tatiana A. ; Subbarao, Kanta ; Barr, Ian G. ; Villanueva, Julie ; Shcherbik, Svetlana ; Bousse, Tatiana ; Rudenko, Larisa G. Less -
Description:
Live attenuated influenza vaccines (LAIVs) are promising tools for the induction of broad protection from influenza due to their ability to stimulate cross-reactive T cells against influenza pathogens. One of the major targets for cytotoxic T-cell immunity is viral nucleoprotein (NP), which is relatively conserved among antigenically distant influenza viruses. Nevertheless, a diversity of epitope composition has been found in the NP protein of different lineages of influenza A viruses. The H2N2 master donor virus which is currently used as a backbone for the LAIV and donor of the six genomic segments encoding the internal proteins, A/Leningrad/134/17/57 (MDV Len/17), was isolated 60 years ago. As such, NP-specific T-cell immunity induced upon vaccination with classical LAIVs with a 6:2 genome composition containing this older NP might be suboptimal against currently circulating influenza viruses. In this study, a panel of H3N2 LAIV candidates with wild-type NP genes derived from circulating viruses were generated by reverse genetics (5:3 genome composition). These viruses displayed the cold adaptation and temperature sensitivity phenotypes of MDV Len/17 in vitro. LAIVs with both 6:2 and 5:3 genome compositions were attenuated and replicated to a similar extent in the upper respiratory tract of ferrets. LAIVs were immunogenic as high neutralizing and hemagglutination inhibition serum antibody titers were detected 21 days after infection. All vaccinated animals were protected against infection with heterologous H3N2 influenza A viruses. Thus, LAIV with a 5:3 genome composition is safe, immunogenic and can induce cross-protective immunity.
Subject:
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Animal Diseases
Animals
Antibodies, Neutralizing
Antibodies, Viral
Article
Disease Models, Animal
Female
Ferrets
Genome, Viral
Immunogenicity, Vaccine
Influenza A Virus
Influenza A Virus, H3N2 Subtype
Influenza Vaccines
Live Attenuated Influenza Vaccine
Male
Neutralization Tests
Nucleoprotein
Nucleoproteins
Orthomyxoviridae Infections
Reverse Engineering
Vaccination
Vaccines, Attenuated

Source:
Infect Genet Evol. 64:95-104
Pubmed ID:
29929009
Pubmed Central ID:
PMC6330673
Document Type:
Journal Article
Funding:
CC999999/Intramural CDC HHS/United States
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:79927a6ae31383c196aa820103faeac290377bd1b8a1f29e24de66ee5bd3e1a0
File Type:

Supporting Files

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