Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs

Abstract

Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth

“…This type of infected animals shed high amounts of virus and are difficult to evaluate from the clinical and anatomopathological point of view. Considering that, persistent infected pigs may go unnoticed in the serological methods used for surveillance, as well as being unresponsive to vaccination (Muñoz‐González, Perez‐Simó, et al., ). Therefore, the detection of this type of infection and its elimination in endemic areas is relevant for global CSF control.…”

“…Considering that, persistent infected pigs may go unnoticed in the serological methods used for surveillance, as well as being unresponsive to vaccination (Muñoz-González, Perez-Simó, et al, 2015).…”

“…IFN‐α concentration in serum was evaluated by ELISA at 0, 7 and 14 days post infection (dpi) (Muñoz‐González, Perez‐Simó, et al., ; Muñoz‐González, Ruggli, et al., ) using monoclonal antibodies (K9 and K17) and IFN‐α recombinant protein (PBL Biomedical Laboratories, Piscataway, NJ, USA). Cytokine concentrations (units/ml) in sera were determined using a regression line built with the optical densities of the cytokine standards used in the test…”

“…IFN-α concentration in serum was evaluated by ELISA at 0, 7 and 14 days post infection (dpi) (Muñoz-González, Perez-Simó, et al, 2015;Muñoz-González, Ruggli, et al, 2015)…”

Virological and Immunological Outcomes of Coinfections

“…In vivo evidence of superinfection exclusion is rare (279)(280)(281). Examples include pigs persistently infected with classical swine fever virus (CSFV), which exclude vaccine strains upon immunization (282). Moreover, persistently infected pigs may also exclude highly virulent CSFV upon challenge infection (279).…”