Development of a Human Lymphatic Filariasis Vaccine, LFGuard for Clinical Testing 2306046

Introduction Lymphatic filariasis (LF) is a neglected tropical disease that causes disability and impairment of the lymphatic system. Millions of people in the endemic area still suffer from LF, even after decades of mass drug administration (MDA). The target of MDA is to block the transmission. A preventive vaccine is needed to eliminate the infection in the endemic countries. Our laboratory developed a tetravalent fusion protein vaccine, rBmHAXT, which demonstrated significant protection and immunogenicity in rodent and non-human primate models. The vaccine has now completed the Good Manufacturing Practice (cGMP) guidelines for use in clinical trials. Methods This study aims to confirm whether the final cGMP product (LFGuard) retains the safety, immunogenicity, and efficacy as observed with the parent vaccine in a mouse model. Three doses of the vaccine were given s/c or I/m along with Al-T4 adjuvant, an alum adsorbed TLR-4 agonist to promote a balanced Th1/Th2 response against the filarial infection. To evaluate safety, we measured the body weight, haematological parameters, liver function, and kidney function. Immunogenicity was determined by evaluating the levels of antigen-specific IgG antibody titer. The vaccine efficacy was determined by a challenge study. Results Our results show that vaccine is safe and has no adverse effects on the body weight, haematological parameters, liver or kidney functions in all vaccinated animals compared to controls irrespective of the route of immunization. All immunized mice showed a high titer of antigen-specific IgG antibodies (1:80,000) in their serum as expected. These mice also had a significantly (p > 0.001) higher number of CD4+ TCM in their spleen. The vaccinated mice also showed significantly higher levels of protection (90.7%) compared to the controls. Conclusion This is the most crucial step in bridging the vaccine to phase I clinical testing. These pre-IND-enabling studies will help bring the LF vaccine close to the clinics.