Immunity & infection
Currently there are no licensed vaccines to control lymphatic filariasis, a tropical parasitic infection that affects 120 million people in 73 countries worldwide. A trivalent rBmHAT fusion protein vaccine developed in our laboratory gave 40% protection against challenge infections in rhesus macaques when given along with alum. In an attempt to improve the vaccine efficacy, in this study we constructed a tetravalent vaccine (rBmHAXT) by combining Bm thioredoxin peroxidase 2 (TPX2) sequences to Bmhat and vaccine potential of rBmHAXT were evaluated in a mouse model. Three different adjuvants formulations were compared to determine the best adjuvant for rBmHAXT. Our results showed that following s/c immunization with four doses of the antigen, all immunized mice developed high titer of antigen-specific serum IgG antibodies. Isotype analysis revealed that alum adjuvanated vaccine promoted only IgG1 antibodies. However, TLR4 agonist (AL019) and mannosylated chitosan (MCA) adjuvanated rBmHAXT induced significant levels of IgG1, IgG2a and IgG2b antibodies. Thus, AL019 and MCA appeared to promote a balanced Th1/Th2 response. Antigen recall response of splenocytes from vaccinated mice showed antigen-specific proliferation and secretion of significant levels of IFN-γ, IL-17 and IL-6. There was also significant increase in the antigen-specific TEM cells in mice vaccinated with rBmHAXT+AL019 and rBmHAXT+MCA. Challenge studies showed that mice vaccinated with rBmHAXT+MCA had maximum parasite killing (82%) compared to the controls (15%). Vaccination with rBmHAXT+alum and rBmHAXT+AL019 showed only 66% and 63.2% parasite killing respectively. These results thus showed that rBmHAXT+MCA is an excellent and improved prophylactic vaccine against lymphatic filariasis.
Post-doctoral Research Associate
university of illinois
Professor of Microbiology and Immunology, Head of
University of Illinois