Lymphatic filariasis affects 120 million people worldwide and another 1.2 billion people are at risk of acquiring the
infection.
Chemotherapy with
mass drug administration is substantially reducing the incidence of the
infection. Nevertheless, an effective
vaccine is needed to prevent the
infection and eradicate the disease. Previously we reported that a multivalent fusion
protein vaccine (rBmHAT) composed of
small heat shock proteins 12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and large extracellular domain of
tetraspanin (TSP LEL) could confer >95% protection against the challenge
infection with Brugia malayi infective larvae (L3) in mouse and gerbil models. In this study we evaluated the immunogenicity and efficacy of rBmHAT fusion
protein vaccine in a rhesus macaque model. Our results show that rBmHAT is highly immunogenic in rhesus macaques. All the vaccinated monkeys developed significant titers of
antigen-specific
IgG antibodies against each of the component
antigens (16,000 for rBmHSP12.6), (24,000 for rBmALT-2) and (16,000 for rBmTSP-LEL). An in vitro antibody dependent cellular cytotoxicity (ADCC) assay performed using the sera samples from vaccinated monkeys showed that the anti-rBmHAT
antibodies are functional with 35% killing of B. malayi L3s. Vaccinated monkeys also had
antigen responding cells in the peripheral blood.
Vaccine-induced protection was determined after challenging the monkeys with 500 B. malayi L3. Following challenge
infection, 3 out of 5 vaccinated macaques failed to develop the
infection. These three protected macaques had high titers of
IgG1 antibodies and their PBMC secreted significantly high levels of IFN-γ in response to the
vaccine antigens. The two vaccinated macaques that picked the
infection had slightly low titers of
antibodies and their PBMC secreted high levels of
IL-10. Based on these findings we conclude that the rBmHAT
vaccine is highly immunogenic and safe and can confer significant protection against challenge
infections in rhesus macaques.