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Background  The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently  Ov -103 and  Ov -RAL-2 are the most promising vaccine candidates against an  Onchocerca volvulus  infection.    Methodology/Principal findings  Protection induced by immunization of mice with the alum-adjuvanted  Ov -103 or  Ov -RAL-2 vaccines appeared to be antibody dependent since AID -/-  mice that could not mount antigen-specific IgG antibody responses were not protected from an  Onchocerca volvulus  challenge. To determine a possible association between antigen-specific antibody responses and anti-larvae protective immunity in humans, we analyzed the presence of anti- Ov -103 and anti- Ov -RAL-2 cytophilic antibody responses (IgG1 and IgG3) in individuals classified as putatively immune, and in infected individuals who developed concomitant immunity with age. It was determined that 86% of putatively immune individuals and 95% individuals with concomitant immunity had elevated IgG1 and IgG3 responses to  Ov -103 and  Ov -RAL-2. Based on the elevated chemokine levels associated with protection in the  Ov -103 or  Ov -RAL-2 immunized mice, the profile of these chemokines was also analyzed in putatively immune and infected individuals; both groups contained significantly higher levels of KC, IP-10, MCP-1 and MIP-1β in comparison to normal human sera. Moreover, human monospecific anti- Ov -103 antibodies but not anti- Ov -RAL-2 significantly inhibited the molting of third-stage larvae (L3)  in vitro  by 46% in the presence of naïve human neutrophils, while both anti- Ov -103 and anti- Ov -RAL-2 antibodies significantly inhibited the molting by 70–80% when cultured in the presence of naive human monocytes. Interestingly, inhibition of molting by  Ov -103 antibodies and monocytes was only in part dependent on contact with the cells, while inhibition of molting with  Ov -RAL-2 antibodies was completely dependent on contact with the monocytes. In comparison, significant levels of parasite killing in  Ov -103 and  Ov -RAL-2 vaccinated mice only occurred when cells enter the parasite microenvironment. Taken together, antibodies to  Ov -103 and  Ov -RAL-2 and cells are required for protection in mice as well as for the development of immunity in humans.    Conclusions/Significance  Alum-adjuvanted  Ov -103 and  Ov -RAL-2 vaccines have the potential of reducing infection and thus morbidity associated with onchocerciasis in humans. The development of cytophilic antibodies, that function in antibody-dependent cellular cytotoxicity, is essential for a successful prophylactic vaccine against this infection.

plos neglected tropical diseases

Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans