Efficacy of emergency vaccination against foot-and-mouth disease in pigs

Since the foot-and-mouth disease epidemics in Europe in 2001 the use of emergency vaccination, if an outbreak occurs, has become more prominent in EU legislation. Since pigs infected with foot-and-mouth disease virus (FMDV) excrete huge amounts of virus they are considered as amplifiers of the disease and therefore the effect of vaccination on pigs is of great interest, especially in areas with high pig density. The aim of this thesis was to establish if and how soon (herd-) immunity in pigs is induced by vaccination and, furthermore, to study the correlation between immune responses after vaccination and protection against challenge. Transmission of FMDV and the effect of vaccination were studied in animal experiments in which half of the pigs were challenged with FMDV and transmission to contact pigs was studied. The outcome of the experiments was quantified using mathematical models. It was shown that, in the used model, pigs were protected against challenge at two weeks after homologous (vaccine virus same as field virus) as well as after heterologous (vaccine virus other than field virus, but within same serotype) vaccination. After challenge at one week after vaccination, transmission to all contact pigs was observed. However, vaccination did lead to a significant reduction of virus excretion after challenge, which will lead to reduction of virus in the environment which will reduce the risk of transmission to other herds. Vaccination with a 4-fold vaccine dose reduced the number of contact infections after challenge at one week after vaccination. Moreover, virus excretion of vaccinated-infected pigs was reduced even more. For decision making regarding control of the disease, it is important that transmission in non-vaccinated and vaccinated pigs is quantified. Quantified transmission parameters can be used in quantitative modelling, which is regarded as an essential tool for developing strategies in preparation of an outbreak and for predicting and evaluating the effectiveness of control policies during an outbreak. In this thesis, estimates for the transmission rate ß, the infectious period T and the reproduction ratio R for both non-vaccinated and vaccinated pigs were quantified with the results of our studies. It was shown that contact structure influenced the transmission rate and that the between-pen transmission-rate was significantly smaller than the within-pen transmission-rate in non-vaccinated pigs. Vaccination reduced ß, T and R of FMDV in pigs as soon as one week post vaccination and for the group vaccinated with a 4-fold vaccine dose R was estimated to be 1, which will probably be sufficient to reduce between-herd transmission sufficiently. Furthermore, it was shown that in individual pigs, the (reduced) virus excretion after infection was correlated with the neutralising antibody-titre at the moment of infection. After vaccination, IgA responses could be demonstrated and an indication that these responses play a possible role in protection against infection was found. After infection, a prolonged IgA response was demonstrated which was previously only described for carrier cattle and therefore needs further investigation. Also, it was demonstrated that after vaccination and infection systemic and mucosal isotype specific immune responses (IgG, IgM and IgA) were comparable. It was concluded that the currently used vaccines are effective in reducing virus transmission as soon as two weeks after vaccination. More research on optimal vaccine composition and dose is recommended. The correlates of protection that were found might be useful in future vaccine-research

Efficacy of emergency vaccination against foot-and-mouth disease in pigs

Since the foot-and-mouth disease epidemics in Europe in 2001 the use of emergency vaccination, if an outbreak occurs, has become more prominent in EU legislation. Since pigs infected with foot-and-mouth disease virus (FMDV) excrete huge amounts of virus they are considered as amplifiers of the disease and therefore the effect of vaccination on pigs is of great interest, especially in areas with high pig density. The aim of this thesis was to establish if and how soon (herd-) immunity in pigs is induced by vaccination and, furthermore, to study the correlation between immune responses after vaccination and protection against challenge. Transmission of FMDV and the effect of vaccination were studied in animal experiments in which half of the pigs were challenged with FMDV and transmission to contact pigs was studied. The outcome of the experiments was quantified using mathematical models. It was shown that, in the used model, pigs were protected against challenge at two weeks after homologous (vaccine virus same as field virus) as well as after heterologous (vaccine virus other than field virus, but within same serotype) vaccination. After challenge at one week after vaccination, transmission to all contact pigs was observed. However, vaccination did lead to a significant reduction of virus excretion after challenge, which will lead to reduction of virus in the environment which will reduce the risk of transmission to other herds. Vaccination with a 4-fold vaccine dose reduced the number of contact infections after challenge at one week after vaccination. Moreover, virus excretion of vaccinated-infected pigs was reduced even more. For decision making regarding control of the disease, it is important that transmission in non-vaccinated and vaccinated pigs is quantified. Quantified transmission parameters can be used in quantitative modelling, which is regarded as an essential tool for developing strategies in preparation of an outbreak and for predicting and evaluating the effectiveness of control policies during an outbreak. In this thesis, estimates for the transmission rate ß, the infectious period T and the reproduction ratio R for both non-vaccinated and vaccinated pigs were quantified with the results of our studies. It was shown that contact structure influenced the transmission rate and that the between-pen transmission-rate was significantly smaller than the within-pen transmission-rate in non-vaccinated pigs. Vaccination reduced ß, T and R of FMDV in pigs as soon as one week post vaccination and for the group vaccinated with a 4-fold vaccine dose R was estimated to be 1, which will probably be sufficient to reduce between-herd transmission sufficiently. Furthermore, it was shown that in individual pigs, the (reduced) virus excretion after infection was correlated with the neutralising antibody-titre at the moment of infection. After vaccination, IgA responses could be demonstrated and an indication that these responses play a possible role in protection against infection was found. After infection, a prolonged IgA response was demonstrated which was previously only described for carrier cattle and therefore needs further investigation. Also, it was demonstrated that after vaccination and infection systemic and mucosal isotype specific immune responses (IgG, IgM and IgA) were comparable. It was concluded that the currently used vaccines are effective in reducing virus transmission as soon as two weeks after vaccination. More research on optimal vaccine composition and dose is recommended. The correlates of protection that were found might be useful in future vaccine-research

A Vaccine Based on the A/ASIA/G-VII Lineage of Foot-and-Mouth Disease Virus Offers Low Levels of Protection against Circulating Viruses from the A/ASIA/Iran-05 lineage

The recent emergence and circulation of the A/ASIA/G-VII (A/G-VII) lineage of foot-and-mouth disease virus (FMDV) in the Middle East has resulted in the development of homologous vaccines to ensure susceptible animals are sufficiently protected against clinical disease. However, a second serotype A lineage called A/ASIA/Iran-05 (A/IRN/05) continues to circulate in the region and it is therefore imperative to ensure vaccine strains used will protect against both lineages. In addition, for FMDV vaccine banks that usually hold a limited number of strains, it is necessary to include strains with a broad antigenic coverage. To assess the cross protective ability of an A/G-VII emergency vaccine (formulated at 43 (95% CI 8–230) PD50/dose as determined during homologous challenge), we performed a heterologous potency test according to the European Pharmacopoeia design using a field isolate from the A/IRN/05 lineage as the challenge virus. The estimated heterologous potency in this study was 2.0 (95% CI 0.4–6.0) PD50/dose, which is below the minimum potency recommended by the World Organisation for Animal Health (OIE). Furthermore, the cross-reactive antibody titres against the heterologous challenge virus were poor (≤log10 0.9), even in those cattle that had received the full dose of vaccine. The geometric mean r1-value was 0.2 (95% CI 0.03–0.8), similar to the potency ratio of 0.04 (95% CI 0.004–0.3). Vaccination decreased viraemia and virus excretion compared to the unvaccinated controls. Our results indicate that this A/G-VII vaccine does not provide sufficient protection against viruses belonging to the A/IRN/05 lineage and therefore the A/G-VII vaccine strain cannot replace the A/IRN/05 vaccine strain but could be considered an additional strain for use in vaccines and antigen banks