Safety, immunogenicity and protection of A(H3N2) live attenuated influenza vaccines containing wild-type nucleoprotein in a ferret model.
Infect Genet Evol
; 64: 95-104, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29929009
ABSTRACT
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 60â¯years ago. As such, NP-specific T-cell immunity induced upon vaccination with classical LAIVs with a 62 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 (53 genome composition). These viruses displayed the cold adaptation and temperature sensitivity phenotypes of MDV Len/17 in vitro. LAIVs with both 62 and 53 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 21â¯days after infection. All vaccinated animals were protected against infection with heterologous H3N2 influenza A viruses. Thus, LAIV with a 53 genome composition is safe, immunogenic and can induce cross-protective immunity.
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MEDLINE
Assunto principal:
Vacinas contra Influenza
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Vacinas Atenuadas
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Infecções por Orthomyxoviridae
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Vírus da Influenza A Subtipo H3N2
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Imunogenicidade da Vacina
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Doenças dos Animais
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Nucleoproteínas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article