Effect of vaccination on transmission of highly pathogenic avian influenza in birds

The increasing magnitude of HPAI epidemics and the endemicy of H5N1 ask for alternative strategies for prevention and control of HPAI next to measures like culling of infected poultry flocks, pre-emptive culling, and the imposement of movement restrictions. Such an alternative is offered by vaccination, which has been applied during some HPAI epidemics. Over the last years, experimental studies have yielded important information about the effect of vaccination on disease symptoms and excretion. However, little is known about the effect of vaccination on transmission, which is crucial when an epidemic has to be controlled by vaccination. The main goal of this thesis was to gain insight in the transmission parameters of HPAI viruses in birds, and in the effect of vaccination on transmission. To this end, transmission experiments with different HPAI strains in unvaccinated and vaccinated birds of different species were performed. To better understand the origin of an HPAI outbreak from an LPAI outbreak, the transmission characteristics of genetically closely related HPAI and LPAI strains (A/Chicken/Pennsylvania/83) from the subtype H5N2 were compared (Chapter 2). The LPAI and HPAI strains appear to differ quite substantially in their key epidemiological parameters, with the HPAI strain spreading more efficiently and having a longer infectious period. In Chapters 3 and 4 the effect of vaccination on transmission of an H7N7 virus that caused a major epidemic in the Netherlands in 2003 was studied. It appears that the effect of vaccination on transmission depends on the bird species, the vaccine, and timing of vaccination relative to the moment of challenge. A single vaccination was able to sufficiently reduce transmission in chickens (Chapter 3), and in teals (Chapter 4), while in pheasants no significant reduction in transmission was observed (Chapter 4). In chickens a difference in the effect of vaccination on transmission was observed between two vaccines that differed in homology and HA content, and between the time points after vaccination (Chapter 3). Chapter 5 elaborates on this theme by focusing on the transmission dynamics of HPAI H5N1 virus in Pekin ducks. The results show that a genetically distant vaccine is able to significantly reduce transmission, although the analyses did not allow us to conclude that transmission is reduced to the extent that no major outbreaks can occur. The results of Chapters 3-5, furthermore, have shown that silent transmission can occur in vaccinated birds. This implies that vaccination programs should be accompanied by monitoring based on a DIVA (Differentiating Infected from Vaccinated Animals) strategy. Therefore, in Chapter 6 three different DIVA tests were validated using sera that were obtained from the experiments in Chapter 3. The analyses show that two serological tests based on a heterologous neuraminidase have sensitivities and specificities of more than 0.90 in detecting antibodies, while the sensitivity in detecting infection is substantially lower. The discrepancy between the sensitivity in detecting antibodies and in detecting infection can be explained by the finding that chickens with no virus excretion or only a short period of virus excretion after infection only have a low probability to develop antibodies