Comparative molecular epidemiology and antigenic characterisation of highly pathogenic avian influenza A(H5) virus in Vietnam

Thesis

Highly pathogenic avian influenza (HPAI) virus poses a significant economic disease burden to the poultry sector of Vietnam, and is a credible threat for emergence of novel zoonotic viruses. This thesis examines the molecular evolution and epidemiology of HPAI A(H5) viruses in Vietnam identified through the national poultry surveillance system. The investigations comprised analysis of detection rates and geographic distribution of A(H5) clade variants from samples collected in live bird markets (LBMs); comprehensive analysis of whole genome sequences of viruses collected from 2012 to 2015; development of laboratory protocols for production of reference chicken antisera; and in-depth antigenic characterisations of contemporary A(H5N1) isolates. The findings underscored the high prevalence and widespread distribution of HPAI A(H5) virus within apparently healthy poultry sampled in LBMs and the difficulties in designing appropriate and effective disease management strategies. Whole genome analysis revealed significant diversification and reassortment of A(H5) viruses, with substantial in-situ evolution of clade 1 and 2.3.4 viruses between 2010 and 2012 and lineage replacements involving clade 2.3.2.1 and 2.3.4.4 viruses during 2014-2015. Antigenic analysis of contemporary A(H5N1) clade variants using chicken antisera produced at the National Center for Veterinary Diagnostics (NCVD) proved to be feasible and reproducible, and recapitulated similar patterns of clade clustering as ferret antisera. Antigenic relationships between existing poultry vaccines and circulating field viruses also appeared aligned with in-vivo vaccine challenge studies, in terms of protection profiles. Given the co-circulation of multiple, antigenically distinct clade variants, there is a great need for vaccine strategies capable of inducing broadly cross-reactive immunity. If traditional inactivated vaccines are used, bivalent or trivalent formulations may be required. The results strongly suggest that antigenic data could ultimately be used as a surrogate (or as a precursor) to challenge studies that take time and resources to conduct, thus potentially enabling more rapid assessments and decisions about poultry vaccine selection by Vietnamese animal health authorities.

Authors: Thi, D

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Molecular, Evolution; Genetic and antigenic diversity of H5 virus in poultry in Vietnam