Immunoprophylaxis in intensive farming systems: the way forward.

High levels of production in intensive farming systems are associated with increased replacement rates as a result of multifactorial diseases. The so-called "production diseases" may include low-grade infection reducing profitability without increased morbidity. Such infections are sustained by low pathogenic viral and bacterial agents which give rise to full-blown disease in association with poor environmental conditions. In these farms, the results of vaccination may be disappointing. Therefore, fundamental issues should be dealt with toward successful immunoprophylaxis. High lean meat and milk production are associated with chronic inflammation and activation of the innate immune system vis-à-vis cellular stress. This may negatively affect adaptive immune responses. A negative modulation of the host microbiome by farm management practices and drug treatments is a further risk factor. The immune response to stressed cells questions the usual correlates of protection investigated after vaccination. In particular, there is evidence that specific and non-specific immune responses may overlap in vitro as a result of a high level of innate immune responses to Damage-Associated Molecular Patterns (DAMPS) and stress antigens. A vigorous adaptive immune response to microbial agents may be sometimes counterproductive, as suggested in porcine reproductive and respiratory syndrome virus (PRRSV) infection. Alternative outcomes should be sometimes pursued: a better homeostatic control of the inflammatory response, effective and self-limiting innate immune responses, and even tolerance induction. On the whole, successful immunoprophylaxis in intensive farming systems demands co-ordinated and multi-disciplinary efforts in terms of animal breeding, farm management and hygiene, correct choice and harmonization of the prophylactic tools (vaccines, immunomodulators, pre- and probiotics). Finally, there is evidence that disease-predicting parameters of the innate immune response may greatly ease the identification of herds and animals at risk, and contribute to reduced antibiotic usage on farm.