title: Shifting Clade Distribution, Reassortment, and Emergence of New Subtypes of Highly Pathogenic Avian Influenza A(H5) Viruses Collected from Vietnamese Poultry from 2012 to 2015.
abstract: Whole-genome sequences of representative highly pathogenic avian influenza A(H5) viruses from Vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from January 2012 to August 2015. Six hemagglutinin gene clades were characterized. Clade 1.1.2 was predominant in southern Mekong provinces throughout 2012 and 2013 but gradually disappeared and was not detected after April 2014. Clade 2.3.2.1c viruses spread rapidly during 2012 and were detected in the south and center of the country. A number of clade 1.1.2 and 2.3.2.1c interclade reassortant viruses were detected with different combinations of internal genes derived from 2.3.2.1a and 2.3.2.1b viruses, indicating extensive cocirculation. Although reassortment generated genetic diversity at the genotype level, there was relatively little genetic drift within the individual gene segments, suggesting genetic stasis over recent years. Antigenically, clade 1.1.2, 2.3.2.1a, 2.3.2.1b, and 2.3.2.1c viruses remained related to earlier viruses and WHO-recommended prepandemic vaccine strains representing these clades. Clade 7.2 viruses, although detected in only low numbers, were the exception, as indicated by introduction of a genetically and antigenically diverse strain in 2013. Clade 2.3.4.4 viruses (H5N1 and H5N6) were likely introduced in April 2014 and appeared to gain dominance across northern and central regions. Antigenic analyses of clade 2.3.4.4 viruses compared to existing clade 2.3.4 candidate vaccine viruses (CVV) indicated the need for an updated vaccine virus. A/Sichuan/26221/2014 (H5N6) virus was developed, and ferret antisera generated against this virus were demonstrated to inhibit some but not all clade 2.3.4.4 viruses, suggesting consideration of alternative clade 2.3.4.4 CVVs.IMPORTANCEHighly pathogenic avian influenza (HPAI) A(H5) viruses have circulated continuously in Vietnam since 2003, resulting in hundreds of poultry outbreaks and sporadic human infections. Despite a significant reduction in the number of human infections in recent years, poultry outbreaks continue to occur and the virus continues to diversify. Vaccination of poultry has been used as a means to control the spread and impact of the virus, but due to the diversity and changing distribution of antigenically distinct viruses, the utility of vaccines in the face of mismatched circulating strains remains questionable. This study assessed the putative amino acid changes in viruses leading to antigenic variability, underscoring the complexity of vaccine selection for both veterinary and public health purposes. Given the overlapping geographic distributions of multiple, antigenically distinct clades of HPAI A(H5) viruses in Vietnam, the vaccine efficacy of bivalent poultry vaccine formulations should be tested in the future.
authors.affiliation: National Center for Veterinary Diagnostics, Department of Animal Health, Hanoi, Vietnam diep.dahvn@gmail.com ctdavis@cdc.gov.|Department of Animal Health, Ministry of Agriculture and Rural Development of Vietnam, Hanoi, Vietnam.|Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.|Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Diep T
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Yunho
authors.initials: Y
authors.lastname: Jang
authors.affiliation: National Center for Veterinary Diagnostics, Department of Animal Health, Hanoi, Vietnam.
authors.forename: Tho D
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Jones
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Shepard
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Gerloff
authors.affiliation: St. Jude's Center for Excellence in Influenza Research and Surveillance, Memphis, Tennessee, USA.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-8960-0728
authors.initials: T
authors.lastname: Fabrizio
authors.affiliation: Department of Animal Health, Ministry of Agriculture and Rural Development of Vietnam, Hanoi, Vietnam.
authors.forename: Long V
authors.initials: LV
authors.lastname: Nguyen
authors.affiliation: Food and Agriculture Organization of the United Nations, Hanoi, Vietnam.
authors.forename: Ken
authors.initials: K
authors.lastname: Inui
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Genyan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Creanga
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Center for Veterinary Diagnostics, Department of Animal Health, Hanoi, Vietnam.
authors.forename: Duong T
authors.initials: DT
authors.lastname: Mai
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Sharmi
authors.initials: S
authors.lastname: Thor
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.affiliation: National Center for Veterinary Diagnostics, Department of Animal Health, Hanoi, Vietnam.
authors.forename: Thanh L
authors.initials: TL
authors.lastname: To
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Wentworth
authors.affiliation: Department of Animal Health, Ministry of Agriculture and Rural Development of Vietnam, Hanoi, Vietnam.
authors.forename: Tung
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Animal Health, Ministry of Agriculture and Rural Development of Vietnam, Hanoi, Vietnam.
authors.forename: Dong V
authors.initials: DV
authors.lastname: Pham
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.|Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Bryant
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA diep.dahvn@gmail.com ctdavis@cdc.gov.
authors.forename: C Todd
authors.initials: CT
authors.lastname: Davis
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D019143:Evolution, Molecular; D015321:Gene Rearrangement; D005814:Genes, Viral; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology*; D058889:Molecular Typing; D010802:Phylogeny; D058974:Phylogeography; D011200:Poultry / Q000821:virology; D017422:Sequence Analysis, DNA; D014744:Vietnam / Q000453:epidemiology
chemical_list: D000956:Antigens, Viral
keywords: Vietnam; antigenicity; evolution; highly pathogenic avian influenza; reassortment; vaccine selection