Emergence of multiple clade 2.3.2.1 influenza A (H5N1) virus subgroups in Vietnam and detection of novel reassortants

Jang

et al. 2017

J Virol

Self Cite

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. IMPORTANCE Highly 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.

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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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

Jang

et al. 2017

J Virol

Self Cite

“…Taken together, the mutations at the antigenic site and the differences in the glycosylation sites on the HA between Dk/ VN/QB1207/12 and the vaccine strains, especially Dk/ Anhui/1/06, may suggest that the current vaccine used in Vietnam cannot protect poultry from infection with genetic variants of clade 2.3.2.1 H5N1 viruses such as Dk/VN/ QB1207/12. The typical peak season for H5N1 outbreak had been during January to February in Vietnam; however, multiple H5N1 outbreaks began in June of 2012, which was possibly related to a decline in protection by H5N1 poultry vaccines against H5N1 viruses, especially variants Virus Genes (2014) 49:278-285 281 of clade 2.3.2.1 viruses, as well as an overall decline in poultry vaccination coverage in Vietnam [19]. Dk/VN/ QB1207/12 was isolated from an outbreak which occurred in July 2012, corresponding to the above-mentioned time frame.…”

Section: Genetic Analysismentioning

confidence: 99%

Genetic characterization of an H5N1 avian influenza virus from a vaccinated duck flock in Vietnam

Bui

Ogawa²,

Trinh³

et al. 2014

Virus Genes

This study reports the genetic characterization of a highly pathogenic avian influenza virus subtype H5N1 isolated from a moribund domestic duck in central Vietnam during 2012. In the moribund duck's flock, within 6 days after vaccination with a commercial H5N1 vaccine (Re-5) to 59-day-old birds, 120 out of 2,000 ducks died. Genetic analysis revealed a substantial number of mutations in the HA gene of the isolate in comparison with the vaccine strains, Re-1 and Re-5. Similar mutations were also found in selected Vietnamese H5N1 strains isolated since 2009. Mutations in the HA gene involved positions at antigenic sites associated with antibody binding and also neutralizing epitopes, with some of the mutations resulting in the modification of N-linked glycosylation of the HA. Those mutations may be related to the escape of virus from antibody binding and the infection of poultry, interpretations which may be confirmed through a reverse genetics approach. The virus also carried an amino acid substitution in the M2, which conferred a reduced susceptibility to amantadine, but no neuraminidase inhibitor resistance markers were found in the viral NA gene. Additional information including vaccination history in the farm and the surrounding area is needed to fully understand the background of this outbreak. Such understanding and expanded monitoring of the H5N1 influenza viruses circulating in Vietnam is an urgent need to provide updated information to improve effective vaccine strain selection and vaccination protocols, aiding disease control, and biosecurity to prevent H5N1 infection in both poultry and humans.

Antigenic characterization of influenza and SARS-CoV-2 viruses

2021

Antigenic characterization of emerging and re-emerging viruses is necessary for the prevention of and response to outbreaks, evaluation of infection mechanisms, understanding of virus evolution, and selection of strains for vaccine development. Primary analytic methods, including enzyme-linked immunosorbent/lectin assays, hemagglutination inhibition, neuraminidase inhibition, micro-neutralization assays, and antigenic cartography, have been widely used in the field of influenza research. These techniques have been improved upon over time for increased analytical capacity, and some have been mobilized for the rapid characterization of the SARS-CoV-2 virus as well as its variants, facilitating the development of highly effective vaccines within 1 year of the initially reported outbreak. While great strides have been made for evaluating the antigenic properties of these viruses, multiple challenges prevent efficient vaccine strain selection and accurate assessment. For influenza, these barriers include the requirement for a large virus quantity to perform the assays, more than what can typically be provided by the clinical samples alone, cell- or egg-adapted mutations that can cause antigenic mismatch between the vaccine strain and circulating viruses, and up to a 6-month duration of vaccine development after vaccine strain selection, which allows viruses to continue evolving with potential for antigenic drift and, thus, antigenic mismatch between the vaccine strain and the emerging epidemic strain. SARS-CoV-2 characterization has faced similar challenges with the additional barrier of the need for facilities with high biosafety levels due to its infectious nature. In this study, we review the primary analytic methods used for antigenic characterization of influenza and SARS-CoV-2 and discuss the barriers of these methods and current developments for addressing these challenges.