Impact of antigenic and genetic drift on the serologic surveillance of H5N2 avian influenza viruses

Abstract

BackgroundSerologic surveillance of Avian Influenza (AI) viruses is carried out by the hemagglutination inhibition (HI) test using reference reagents. This method is recommended by animal health organizations as a standard test to detect antigenic differences (subtypes) between circulating influenza virus, vaccine- and/or reference- strains. However, significant discrepancies between reference antisera and field isolates have been observed during serosurveillance of influenza A viruses in pig and poultry farms. The objective of this study was to examine the effects of influenza virus genetic and antigenic drift on serologic testing using standard HI assays and reference reagents. Low pathogenic AI H5N2 viruses isolated in Mexico between 1994 and 2008 were used for phylogenetic analysis of AI hemagglutinin genes and for serologic testing using antisera produced with year-specific AI virus isolates.ResultsPhylogenetic analysis revealed significant divergence between early LPAI H5N2 viruses (1994 - 1998) and more recent virus field isolates (2002 - 2008). Results of the HI test were markedly influenced by the selection of the AI H5N2 virus (year of isolation) used as reference antigen for the assay. These analyses indicate that LPAI H5N2 viruses in Mexico are constantly undergoing genetic drift and that serosurveillance of AI viruses is significantly influenced by the antigen or antisera used for the HI test.ConclusionsReference viral antigens and/or antisera need to be replaced constantly during surveillance of AI viruses to keep pace with the AI antigenic drift. This strategy should improve the estimation of antigenic differences between circulating AI viruses and the selection of suitable vaccine strains.

Getting More Out of Less – A Quantitative Serological Screening Tool for Simultaneous Detection of Multiple Influenza A Hemagglutinin-Types in Chickens

“…Failure to regularly update antigens in HI-assay can result in a reduced ability to detect antibodies against more recent field isolates [27] and it is unclear if this also can be observed in our assay system. The strains used for the infections of group 2 animals were closely related to the strains from which antigens were produced, with the lowest level of AA-identity for antigen H9.07 (94.4%) (Table 3).…”

The emergence and diversification of panzootic H5N1 influenza viruses

“…The impact of vaccination on virus evolution has been observed during H5N2 outbreaks in Mexico, where 2 billion doses of vaccine were administered from 1995–2008 (Eggert et al, 2010). Despite this vaccination program LPAI H5N2 viruses have continued to circulate in Mexico for almost 20 years, with spread to neighboring countries (Escorcia et al, 2010; Lee et al, 2004). It is thought that the long-term use of H5N2 vaccines in poultry has led to antigenic drift and diversification of LPAI H5N2 viruses away from the vaccine strain, with challenge experiments showing that the vaccine was unable to prevent shedding of LPAI H5N2 virus (Escorcia et al, 2010; Lee et al, 2004).…”

“…Despite this vaccination program LPAI H5N2 viruses have continued to circulate in Mexico for almost 20 years, with spread to neighboring countries (Escorcia et al, 2010; Lee et al, 2004). It is thought that the long-term use of H5N2 vaccines in poultry has led to antigenic drift and diversification of LPAI H5N2 viruses away from the vaccine strain, with challenge experiments showing that the vaccine was unable to prevent shedding of LPAI H5N2 virus (Escorcia et al, 2010; Lee et al, 2004). There are therefore striking parallels with the HPAI H5N1 situation, and it is therefore possible that the large-scale vaccination programs in China, Egypt and Indonesia may have contributed to the antigenic drift of circulating viruses.…”

Evaluation of enzyme-linked immunosorbent assays and a haemagglutination inhibition tests for the detection of antibodies to Newcastle disease virus in village chickens using a Bayesian approach

“…While the former test specifically detects antibodies directed against epitopes of the haemagglutinin neuraminidase protein of APMV-1, the ELISA detects mostly a wider spectrum of antibodies specific for different viral proteins , unless designed to detect specific antibodies against a selected structural protein. Furthermore, it has been observed, in avian influenza diagnosis, that the performance of HI test is strongly influenced by the homology or relatedness between the reference viral antigens and the virus isolate or antibodies to be tested (Escorcia et al, 2010) and this may be equally valid for NDV. Blocking antibodies developed against the PMV-1 epitope, like the one used in the bELISA, are specific for the NDV infection in any host and at any age (Koch et al, 1998).…”