Tu183 - Bridging Studies with cGMP RBmHAXT(∆cys), a Tetravalent Vaccine for Lymphatic Filariasis, for Clinical Development

Abstract Text: Lymphatic Filariasis (LF), a chronic parasitic infection caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori, results in severe lymphatic dysfunction, leading to debilitating limb, breast, and genital edema. Although prophylactic administration of antiparasitic drugs has been used since 2000, disease transmission persists with irreversible lymphatic damage in patients globally. There is currently no vaccine available to protect the vulnerable population. Our laboratory previously developed a tetravalent vaccine, rBmHAXT(∆cys) that completed all pre-clinical studies, product development, and GMP manufacturing. Before initiating the clinical trials, there is a need to perform bridging experiments with the GMP rBmHAXT(∆cys) to confirm the vaccine efficacy and potency. Thus, in this study, we compared the immunogenicity and vaccine-induced protection of GMP rBmHAXT(∆cys) (three engineering runs) with our parent rBmHAXT(∆cys) protein in a mouse model. Our results show that the GMP rBmHAXT(∆cys) induced high titers (>1:40,000) of IgG antibodies and memory T cell responses to rBmHAXT(∆cys) that are comparable to the responses following immunization with the parent vaccine antigen. The vaccine-induced protection in GMP rBmHAXT(∆cys) immunized mice was (90.7 + 9.67%), which was similar to the protection seen in mice immunized with the parent protein (93.7 + 9.67%) and significant compared to control. These studies confirmed that the GMP protein retained the vaccine potential of the parent protein. These pre-IND-enabling studies will help bring the LF vaccine close to the clinics and aid in preventing the infection in 846 million people who are at risk of being infected in 52 endemic countries around the world.