Trained immunity is not universal: oral heat-inactivated Mycobacterium bovis confers no protection against the non-enveloped Porcine Circovirus 2

Abstract Background Trained immunity, the enhanced response of innate cells leading to an improved innate immune response, and antibodies against the glycan galactose-α-1,3-galactose (α-Gal), produced by animals unable to synthesize α-Gal epitopes, have been suggested to provide the host certain advantage in infections with enveloped viruses. Conversely, the evidence of protection against non-enveloped viruses attributed to the referred mechanisms remains scarce. Aiming to evaluate whether a heat-inactivated Mycobacterium bovis (HIMB) immunostimulant, which had proven to protect against related and non-related pathogens, confers an advantage against non-enveloped viruses, we performed an immunization and challenge experiment with porcine circovirus 2 (PCV-2) in swine. Sixteen piglets were randomly assigned to the immunized group (n = 8), which received two oral doses of HIMB with an interval of three weeks, or to the control group (n = 8). All animals were infected by intranasal inoculation with PCV-2 21 days later and euthanized at day 21 post-challenge. Results No differences in body weight and body temperature, viremia and viral burden in target tissues, antibody production and histopathological changes in target tissues were observed between the immunized and the control group. Overall, oral immunization with HIMB did not protect pigs against PCV-2 infection. Conclusions Our study suggests that HIMB confers no advantage against pathogens lacking α-Gal, mainly non-enveloped viruses such as PCV-2, in α-Gal-producing hosts, such as the swine.