Evaluation of protective immunity of Leptospira immunoglobulin like protein A (LigA) DNA vaccine against challenge in hamsters

Abstract

We demonstrated earlier that immunization with recombinant Leptospira immunoglobulin like protein A (LigA) induced significant protection against virulent Leptospira interrogans serovar Pomona challenge in hamsters. However, the protective immune mechanism remains unclear. In the present study we demonstrated the protective efficacy of a LigA DNA vaccine and evaluated the immune mechanism underlying the protection against leptospirosis in hamsters. The LigA DNA vaccine was constructed in two truncated forms as the conserved portion (LigAcon) and a variable portion (LigAvar). Four-week-old hamsters were immunized three times at two-week intervals with vector alone or an equal amount of a recombinant construct containing either LigAcon or LigAvar. All animals were challenged intraperitoneally 2 weeks after the last immunization with a dose (LD 50 = 10 8) of virulent L. interrogans serovar Pomona. Prior to challenge, four animals were sacrificed, the spleen was removed aseptically, and splenocytes were assayed for lymphocyte proliferation and cytokine profiles in response to recall antigen. The protective efficacy was evaluated on the basis of survival and histopathological lesions in the kidney. The immuno-protective mechanism was assessed on the basis of Th1/Th2 profile of cytokines in immunized animals. Our results indicate that immunization with LigA DNA vaccine provides significant protection against leptospirosis. We suggest that immuno-protection is conferred by both humoral and cellular immunity as revealed by an increase in antibody titers during subsequent boosters, significant proliferation of lymphocytes and enhancement of both Th1 and Th2 cytokines. Taken together, the present study suggests that a LigA DNA vaccine is a promising candidate for prevention of leptospirosis.