Enhancing the Immunoprophylactic efficacy of a filarial vaccine candidate abundant larval transcript 2 by lipid modification

Abstract

Human lymphatic filariasis, a neglected tropical disease, is a debilitating and disfiguring mosquito-borne parasitic disease. This morbid disease is caused by the filarial worms Wuchereria bancrofti, Brugia malayi and Brugia timori, whose life cycle is quite complex with five developmental stages, in two different hosts. In the mammal host, the adult female worms produce microfilariae (mf), which undergo two developmental changes in the feeding mosquito vector to form infective larvae (L3) that are inoculated back into the vertebrate host by another insect bite where the final two stages of development take place. Though it is not an easy task to generate a vaccine against a multicellular parasite, filarial vaccine has long been on the wish list of scientists because it might become the only useful tool, should resistance develop against the currently used anti-filarial drugs like Diethyl Carbamazine (DEC), Albendazole and Ivermectin. Despite the important role of adjuvants, relatively few adjuvants have been successfully incorporated into vaccines intended for human administration, owing in part due to their high toxicity. The stability of vaccines has a major impact on the success of immunization and for vaccines under development, the appropriateness of thermal stability should be explored. The accelerated as well as real-time stability studies have demonstrated that the LALT protein has comparatively excellent stability than SALT and NALT proteins at room temperature as well as elevated temperatures. Hence, the lipid modification of filarial ALT-2 protein, which enhances its immunoprophylactic activity even in the absence of its significant signal sequence, is also a better option for increasing its stability, making the lipid modified ALT-2 well adapted for storage and maintenance than the native forms. newline