Vaccine Control of Avian Influenza H5N1 in Poultry: Need for a Positive Marker

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 virus strains have emerged as zoonotic viral pathogens over the last decade and have eluded our serious attempts of control in domestic poultry by vaccination, with numerous countries continuing to have epidemic waves. Although the biology and genomics of H5N1 influenza viruses are well characterized so far, viral outbreaks still occur in domestic poultry, posing a dangerous threat of human transmission. There are two main types of contemporary inactivated vaccines, namely whole virus vaccines and virus vaccines engineered by reverse genetics, both of which are administered with adjuvant to hatchlings and optimally require a booster. However, determinants of vaccine efficacy need to be considered distinctly in chickens versus ducks on a country basis. There is a critical need for detection of infection and vaccination of domestic poultry to control potentially deadly but silent infection in vaccinated flocks. A positive vaccine marker strategy using tetanus toxoid offers advantages for more effective control programs of HPAI including improved capacity for early detection of virus outbreaks and indisputable data for surveillance of vaccinated flocks in vaccination control programs for backyard and village poultry, highly desirable in endemic regions. A DIVA strategy that has been developed for use in Europe exploits a H5N2 vaccine containing a heterologous NA antigen to the circulating H5N1 avian influenza virus [11]. The heterologous NA DIVA approach is based on detection of animals with positive anti-N1 antibody responses before a detectable rise in the flock H5 antibody levels but the anamnestic response in vaccinated poultry to H5 will develop more rapidly than the primary antibody response to N1. Thus, a primary antibody response to the different N subtype to that given in the vaccine takes a longer time to develop than a recall memory antibody response to the H5 antigen, allowing unmonitored virus spread throughout the flock. Current guidelines for serological DIVA testing in Europe, requiring only small sample sizes of 5-10 birds tested for NA antibody, would only provide assurance of detecting infection at the 95% confidence level if over 30% of poultry in the flock have been exposed to field virus [12]. This would likely take at least 3 weeks from introduction of infection to allow detection (one week for the virus to infect sufficient numbers of birds in the flock and a further 2 weeks for development of primary antibody responses in infected birds), a time when infection may no longer be active in the flock [13]. Not all exposed vaccinated poultry will develop antibodies to N1 in the virulent field strain due to limited replication in vaccinated animals [14]. Use of homologous NA antigens in vaccines, particularly for ducks, precludes use of the anti-N1 DIVA strategy. Other DIVA approaches for poultry based on negative markers include anti-NS1 and anti-NP antibody testing for recombinant live virus vector vaccines [15], including rHVT-H5, rNDV-H5 a...

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