Porcine Reproductive and Respiratory Syndrome (PRRS) is a chronic and economically important viral disease of pigs. Currently available PRRS virus (PRRSV) vaccines have been administered systemically (intramuscular injection) and they failed to completely protect against reinfections, and absolutely no protection against non-identical PRRS viruses. The aim of this project was to identify potent bacterial based mucosal adjuvants for development of protective anti-PRRSV immunity in pigs. It has been confirmed that effective anti-viral mucosal immunity prevents entry of pathogen in to the body and protects against homologous as well as heterologous infections. But to achieve that goal we need help from suitable adjuvants. Adjuvant is any agent that helps to elicit adequate specific immune responses to vaccine antigens. The PRRSV principally infects lung, therefore we performed all our inoculations by intranasal route (IN) to generate anti-PRRSV specific mucosal immunity. We performed extensive search for suitable adjuvants inoculated IN along with modified live PRRSV vaccine (PRRSV-MLV) (RespPRRS®, Boehringer Ingelheim) in pigs. Out of nine candidate adjuvants that we tested, adjuvanticity of three of them were favorable to generate both anti-PRRSV mucosal (local) and systemic immunity. Further, in our challenge studies pigs were immunized with PRRSV-MLV along with one of the three potent adjuvants (Mycobacterium tuberculosis whole cell lysate), and then challenged with homologous or heterologous PRRSV, I/N. Our results detected a significant rescue in the body weight loss, reduced viral load, reduction in lung pathology, reduced fever, supported by favorable anti-PRRSV mucosal and systemic immune responses in mucosally immunized and virulent PRRSV challenged pigs. Thus, we conclude that protective anti-PRRSV mucosal immunity is critical to control PRRSV outbreaks and that could be achieved when conventional PRRSV-MLV administered along with suitable adjuvants, intransally.