SXP-RAL Family Filarial Protein, rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis.

Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP-RAL family protein of Wuchereria bancrofti i.e. rWbL2 protein in DSS induced inflammatory ulcerative colitis in a mouse model. Prior treatment of rWbL2, followed by induction of colitis, showed significantly reduced disease severity as indicated by the decreased disease manifestations and improved macroscopic and microscopic inflammation. This preventive effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-17 by the splenocytes of treated mice. From this study, it can be envisaged that pretreatment with filarial protein, rWbL2, can prevent the establishment of ulcerative colitis in BALB/c mice. The underlying immunological mechanism may involve the up-regulation of Th2 immune response with down-regulation of Th1 response.

Improving the efficacy of a prophylactic vaccine formulation against lymphatic filariasis.

Mass drug administration (MDA) is the current strategy for interrupting the transmission of lymphatic filariasis (LF) infection and control of the disease in endemic areas. However, subject non-compliance has resulted in the presence of several "transmission hotspots" in the endemic regions threatening the reemergence of LF. This situation is further complicated by the fact that the drugs used in MDA are not effective against adult LF worms, a major concern for the control strategy. Thus, there is clearly a need for an effective and sustainable approach to control LF. Prophylactic vaccine combined with targeted treatment of infected patients and vector control is suggested as a more sustainable strategy to eliminate LF infection from endemic regions. A multivalent vaccine (rBmHAT) developed in our laboratory conferred about 90% protection in rodents. However, when we tested the rBmHAT vaccine along with alum in rhesus macaques, only about 40% protection was achieved and the immune response obtained was Th2 biased. In an attempt to improve the vaccine, in this study, we tested two vaccine antigens (rBmHAT and rBmHAX) along with two adjuvant formulations [alum + GLA (AL019) and mannosylated chitosan (MCA)] in a mouse model. Our results show that rBmHAT is a better vaccine antigen than rBmHAX. Combination of rBmHAT with AL019 or MCA adjuvants gave 94 and 88% protection, respectively, against challenge infections. Immunized animals developed antigen-specific memory T cells that secreted significant levels of IL-4, IFN-γ, and IL-17 suggesting the generation of a balanced Th1/Th2 responses following immunization. A major advantage of MCA adjuvant is that the vaccine booster doses can be administered orally. These studies thus showed that rBmHAT is a better vaccine antigen and can be given in combination with AL019 or MCA adjuvant to obtain excellent results.