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Lymphatic filariasis affects nearly 120 million people worldwide and mass preventive chemotherapy is currently used as a strategy to control this infection. This has substantially reduced the incidence of the infection in several parts of the world. However, a prophylactic vaccine would be more effective in preventing future infections and will supplement the mass chemotherapy efforts. Unfortunately, there is no licensed vaccine available currently to prevent this infection. Molecules expressed on the surface of the parasite are potential candidates for vaccine development as they are exposed to the host immune system. In this study we show that the large extracellular loop of tetraspanin (TSP LEL), a protein expressed on the cuticle of  Brugia malayi  and  Wuchereria bancrofti  is a potential vaccine candidate. Our results showed that  Bm TSP LEL is expressed on the surface of  B. malayi  infective third stage larvae (L3) and sera from human subjects who are putatively immune to lymphatic filariasis carry high titer of IgG1 and IgG3 antibodies against  Bm TSP LEL and  Wb TSP LEL. We also showed that these antibodies in the sera of human subjects can participate in the killing of  B. malayi  L3 in an antibody dependent cell-mediated cytotoxicity mechanism. Vaccination trials in mice showed that close to 64% protection were achieved against challenge infections with  B. malayi  L3. Immunized animals showed high titer of anti- Wb TSP LEL IgG1, IgG2a and IgG2b antibodies in the sera and IFN-γ secreting cells in the spleen.  Onchocerca volvulus  another filarial parasite also expresses TSP LEL. Cross-reactivity studies showed that IgG1 antibody in the sera of endemic normal subjects, recognize  Ov TSP LEL. Similarly, anti- Ov TSP LEL antibodies in the sera of subjects who are immune to  O. volvulus  were also shown to cross-react with r Wb TSP LEL and r Bm TSP LEL. These findings thus suggested that rTSP LEL can be developed as a potential vaccine candidate against multiple filarial infections.

Large Extracellular Loop of Tetraspanin as a Potential Vaccine Candidate for Filariasis