Neonatal vaccination with Mycobacterium bovis BCG: Potential effects as a priming agent shown in a heterologous prime-boost immunization protocol

In general prime-boost immunization including Mycobacterium bovis bacille Calmette-Guérin (BCG) as a priming agent has been a recent successful strategy in animal models. However, the effects of BCG as a priming vaccine have not been investigated systematically. Thus, we modelled a heterologous prime-boost immunization in mice with BCG administered at the neonatal period and mycobacterial heparin-binding hemagglutinin (HBHA) at adult ages. Mice were challenged with a high dose of BCG (107 colony forming units) via intranasal (i.n.) route. We addressed whether the route of administration and addition of adjuvants could be of importance in HBHA-immunizations while animals were primed with BCG. Our results showed that prime-boost immunization induced significantly higher levels of protection in animals compared to the group vaccinated with BCG alone. Most importantly, the levels of protection were comparable between the i.n. and subcutaneous (s.c.) boostings with native (n) HBHA and the coadministration of adjuvant was not necessary. Moreover, priming with BCG improved also the protection promoted by the recombinant form of HBHA, even if to a lower degree to that observed after nHBHA boosting. In general, vaccination with BCG prior to the HBHA administration was found to contribute in two ways: it primed the immune system and provided adjuvant effect. We discuss the several outcomes following neonatal BCG priming and HBHA boosting for better protection against tuberculosis.