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Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity.
Vaccine. 2015 Jun 22; 33(28):3186-92.V

Abstract

The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have caused 343 documented cases of human infection linked to contact with swine. An effective vaccine is needed for these viruses, which may acquire transmissibility among humans. However, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs while preserving their immunizing effectiveness. After serial passage of a representative H3N2v isolate (A/Indiana/08/2011), we identified several egg-adaptive combinations of HA mutations and assessed the egg-based replication, antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6+2 reverse genetics CVVs carrying these mutations. Here we demonstrate that the respective combined HA substitutions G1861V+N2461K, N1651K+G1861V, T1281N+N1651K+R762G, and T1281N+N1651K+I102M, all identified after egg passage, enhanced the replication of the CVVs in eggs without substantially affecting their antigenicity or immunogenicity. The mutations were stable, and the mutant viruses acquired no additional substitutions during six subsequent egg passages. We found two crucial mutations, G186V, which was previously defined, and N246K, which in combination improved virus yield in eggs without significantly impacting antigenicity or immunogenicity. This combination of egg-adaptive mutations appears to most effectively generate high egg-based yields of influenza A/Indiana/08/2011-like CVVs.

Authors+Show Affiliations

Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA. Electronic address: subrata.barman@stjude.org.Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA. Electronic address: john.franks@stjude.org.Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA. Electronic address: jasmine.turner@stjude.org.Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA; Viral Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB) , 125 Gwahak-ro, Youseong-gu, Daejeon, 305-806, South Korea. Electronic address: syoon@kribb.re.kr.Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA. Electronic address: robert.webster@stjude.org.Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 330, Memphis, TN, 38105-3678, USA. Electronic address: richard.webby@stjude.org.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25999284

Citation

Barman, Subrata, et al. "Egg-adaptive Mutations in H3N2v Vaccine Virus Enhance Egg-based Production Without Loss of Antigenicity or Immunogenicity." Vaccine, vol. 33, no. 28, 2015, pp. 3186-92.
Barman S, Franks J, Turner JC, et al. Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity. Vaccine. 2015;33(28):3186-92.
Barman, S., Franks, J., Turner, J. C., Yoon, S. W., Webster, R. G., & Webby, R. J. (2015). Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity. Vaccine, 33(28), 3186-92. https://doi.org/10.1016/j.vaccine.2015.05.011
Barman S, et al. Egg-adaptive Mutations in H3N2v Vaccine Virus Enhance Egg-based Production Without Loss of Antigenicity or Immunogenicity. Vaccine. 2015 Jun 22;33(28):3186-92. PubMed PMID: 25999284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity. AU - Barman,Subrata, AU - Franks,John, AU - Turner,Jasmine C, AU - Yoon,Sun-Woo, AU - Webster,Robert G, AU - Webby,Richard J, Y1 - 2015/05/18/ PY - 2015/02/11/received PY - 2015/04/24/revised PY - 2015/05/03/accepted PY - 2015/5/23/entrez PY - 2015/5/23/pubmed PY - 2016/3/16/medline KW - Antigenicity KW - Egg adaptation KW - Hemagglutinin H3 mutations KW - Immunogenicity KW - Influenza A virus KW - Vaccine virus KW - Variant virus KW - Zoonosis SP - 3186 EP - 92 JF - Vaccine JO - Vaccine VL - 33 IS - 28 N2 - The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have caused 343 documented cases of human infection linked to contact with swine. An effective vaccine is needed for these viruses, which may acquire transmissibility among humans. However, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs while preserving their immunizing effectiveness. After serial passage of a representative H3N2v isolate (A/Indiana/08/2011), we identified several egg-adaptive combinations of HA mutations and assessed the egg-based replication, antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6+2 reverse genetics CVVs carrying these mutations. Here we demonstrate that the respective combined HA substitutions G1861V+N2461K, N1651K+G1861V, T1281N+N1651K+R762G, and T1281N+N1651K+I102M, all identified after egg passage, enhanced the replication of the CVVs in eggs without substantially affecting their antigenicity or immunogenicity. The mutations were stable, and the mutant viruses acquired no additional substitutions during six subsequent egg passages. We found two crucial mutations, G186V, which was previously defined, and N246K, which in combination improved virus yield in eggs without significantly impacting antigenicity or immunogenicity. This combination of egg-adaptive mutations appears to most effectively generate high egg-based yields of influenza A/Indiana/08/2011-like CVVs. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/25999284/Egg_adaptive_mutations_in_H3N2v_vaccine_virus_enhance_egg_based_production_without_loss_of_antigenicity_or_immunogenicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(15)00632-5 DB - PRIME DP - Unbound Medicine ER -