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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.

Developing an effective vaccine against lymphatic filariasis will complement the WHO's effort to eradicate the infection from endemic areas. Currently 83 different countries are endemic for this infection and over 1 billion people are at risk. An effective vaccine coupled with mass drug administration will reduce the morbidity and social stigma associated with this gruesome disease. Several potential vaccine candidates that can confer partial protection in experimental animals have been reported from different laboratories. However, no licensed vaccines are currently available for this disease. Among the several vaccine antigens identified from our laboratory, three most promising antigens; rBmHSPαc (α crystalline domain and c-terminal extension of Heat Shock Protein 12.6), rBmALT-2 (Abundant larval transcript) and rBmTSP LEL (Tetraspanin large extracellular loop) was further developed as a recombinant fusion protein vaccine (rBmHATαc). In a mouse model this fusion protein vaccine gave close to 68% protection following a challenge infection. To improve the vaccine efficiency of rBmHATαc, in this study we evaluated various preparations of alum (AL007, AL019, Alhydrogel and Imject® Alum) as adjuvants. Our results show that mice immunized with rBmHATαc formulated in AL007 (alum from IDRI) and/or AL019 (alum plus TLR-4 agonist from IDRI) gave the highest IgG antibody titer compared to other groups. Subsequent in vivo challenge experiments confirmed that >95% protection can be achieved when AL007 or AL019 was used as the adjuvant. However, when Imject® Alum or alhydrogel was used as the adjuvant only 76% and 72% protection respectively could be achieved. These results show that AL007 or AL019 (IDRI) is an excellent choice of adjuvant for the rBmHATαc vaccine against B. malayi L3 in mice., (Copyright © 2013 Elsevier Ltd. All rights reserved.)