Role of Vaccination-Induced Immunity and Antigenic Distance in Transmission Dynamics Investigated Using Highly Pathogenic Avian influenza (HPAI) H5N1 Virus Escape Mutants

Evolution of avian influenza viruses – especially of the highly pathogenic avian influenza (HPAI) H5N1 subtype – is a major issue, since HPAI H5N1 epidemics are associated with huge economic losses and connected to human morbidity and mortality. Vaccination as a means to prevent transmission has oftentimes been reported as being ineffective and as a potential driving force in the selection of immune escape mutants. In order to improve vaccination efficiency therefore, it is essential to study and quantify how vaccine dose and antigenic distance between vaccine and field strains may affect transmission. To this effect we use mutants selected under pressure from homologous polyclonal sera and their parent strains to study the role of vaccine dose and antigenic distance between vaccine and challenge strains in the transmission dynamics of these strains. We have conducted transmission experiments in chickens vaccinated with high and low doses of selected immune escape mutants. Our results show that the level of vaccination-induced haemagglutination inhibition (HI) titre is the single most important factor in determining whether transmission of the challenge strains takes place in a vaccinated population. We demonstrate that antigenic distance between vaccine and challenge strains is not a major factor in the transmission dynamics of the strains used, since the effect of vaccination dose on HI titre is much larger than the effect of antigenic distance on HI titre. The reduction in transmission due to animals with higher HI titres is caused by lower infectivity and not lower susceptibility.