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The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response.
Vaccine. 2010 May 28; 28(24):4079-85.V

Abstract

Influenza H3N2 viruses have recently drifted from A/Wisconsin/67/05-like to A/Brisbane/10/07-like viruses. The effect of key amino acid substitutions in the hemagglutinin (HA) protein on the replication, antigenicity and immunogenicity of cold-adapted, live attenuated vaccine strains was examined. A/Brisbane/10/07 egg isolate contained a unique combination of G186 and P194 which were required for efficient virus growth in Madin-Darby Canine Kidney (MDCK) cells and embryonated chicken eggs, but the virus induced low level of serum antibody response in ferrets. Substitution of the G186 and P194 in the HA of A/Brisbane/10/07 by V186 and L194 that were present in the HA of A/Wisconsin/67/05-like viruses significantly impaired virus replication but greatly improved the immunogenicity of the vaccine virus to a level comparable to that elicited by the A/Wisconsin/67/05 vaccine. The replication of the variants with impaired growth could be improved by amino acid substitutions at the 195 or 226 residues. The viruses with the G186 and P194 residues were antigenically distinct from the viruses with V186 and L194. Sequence analysis of the HA sequences of the H3N2 viruses from the database and sequencing of the HA gene of a cell-derived A/Brisbane/10/07-like virus before and after egg passage indicated that the P194 residue was most likely derived from egg adaptation. Our results demonstrated the importance of careful evaluation of vaccine strains to ensure that the selected vaccines not only replicate well in eggs, but also retain their antigenicity and are immunogenic in the host.

Authors+Show Affiliations

MedImmune, 297 North Bernardo Avenue, Mountain View, CA 94043, USA. chenz@medimmune.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20399830

Citation

Chen, Zhongying, et al. "The Impact of Key Amino Acid Substitutions in the Hemagglutinin of Influenza a (H3N2) Viruses On Vaccine Production and Antibody Response." Vaccine, vol. 28, no. 24, 2010, pp. 4079-85.
Chen Z, Zhou H, Jin H. The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response. Vaccine. 2010;28(24):4079-85.
Chen, Z., Zhou, H., & Jin, H. (2010). The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response. Vaccine, 28(24), 4079-85. https://doi.org/10.1016/j.vaccine.2010.03.078
Chen Z, Zhou H, Jin H. The Impact of Key Amino Acid Substitutions in the Hemagglutinin of Influenza a (H3N2) Viruses On Vaccine Production and Antibody Response. Vaccine. 2010 May 28;28(24):4079-85. PubMed PMID: 20399830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response. AU - Chen,Zhongying, AU - Zhou,Helen, AU - Jin,Hong, PY - 2009/12/01/received PY - 2010/03/24/revised PY - 2010/03/26/accepted PY - 2010/4/20/entrez PY - 2010/4/20/pubmed PY - 2010/8/28/medline SP - 4079 EP - 85 JF - Vaccine JO - Vaccine VL - 28 IS - 24 N2 - Influenza H3N2 viruses have recently drifted from A/Wisconsin/67/05-like to A/Brisbane/10/07-like viruses. The effect of key amino acid substitutions in the hemagglutinin (HA) protein on the replication, antigenicity and immunogenicity of cold-adapted, live attenuated vaccine strains was examined. A/Brisbane/10/07 egg isolate contained a unique combination of G186 and P194 which were required for efficient virus growth in Madin-Darby Canine Kidney (MDCK) cells and embryonated chicken eggs, but the virus induced low level of serum antibody response in ferrets. Substitution of the G186 and P194 in the HA of A/Brisbane/10/07 by V186 and L194 that were present in the HA of A/Wisconsin/67/05-like viruses significantly impaired virus replication but greatly improved the immunogenicity of the vaccine virus to a level comparable to that elicited by the A/Wisconsin/67/05 vaccine. The replication of the variants with impaired growth could be improved by amino acid substitutions at the 195 or 226 residues. The viruses with the G186 and P194 residues were antigenically distinct from the viruses with V186 and L194. Sequence analysis of the HA sequences of the H3N2 viruses from the database and sequencing of the HA gene of a cell-derived A/Brisbane/10/07-like virus before and after egg passage indicated that the P194 residue was most likely derived from egg adaptation. Our results demonstrated the importance of careful evaluation of vaccine strains to ensure that the selected vaccines not only replicate well in eggs, but also retain their antigenicity and are immunogenic in the host. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/20399830/The_impact_of_key_amino_acid_substitutions_in_the_hemagglutinin_of_influenza_A__H3N2__viruses_on_vaccine_production_and_antibody_response_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(10)00478-0 DB - PRIME DP - Unbound Medicine ER -