Abstract
Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle.Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs.Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4–5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine α1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge.Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-γ responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge.Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.
Highlights
Observational studies and randomized controlled trials in humans have shown that many childhood vaccines can affect resistance to other infections than the targeted disease; a phenomenon called non-specific effects of vaccines or heterologous immunity [1]
The vaccine was immunogenic in the pigs as evidenced by increased IFN-γ responses to purified protein derivative of Mycobacterium paratuberculosis
The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge
Summary
Observational studies and randomized controlled trials in humans have shown that many childhood vaccines can affect resistance to other infections than the targeted disease; a phenomenon called non-specific effects of vaccines or heterologous immunity [1]. Non-live vaccines like the inactivated diphtheria-pertussis-tetanus vaccine may have negative non-specific effects [5]. The evidence from epidemiological and immunological studies in humans has been corroborated by experimental animal models, in mice [7], very few studies have investigated potential non-specific effects of veterinary vaccines, despite the fact that veterinary vaccines are administered routinely in virtually all commercial animal production systems to an increasing number of animals. If veterinary vaccines have non-specific effects, there may be potential to optimize the current use of vaccines to production animals, thereby reducing mortality and morbidity, antibiotics use and the implicated financial losses. Recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle
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