Outer membrane protein complex as a carrier for malaria transmission blocking antigen Pfs230

Abstract

Malaria transmission blocking vaccines (TBV) target the mosquito stage of parasite development by passive immunization of mosquitoes feeding on a vaccinated human. Through uptake of vaccine-induced antibodies in a blood meal, mosquito infection is halted and hence transmission to another human host is blocked. Pfs230 is a gametocyte and gamete surface antigen currently under clinical evaluation as a TBV candidate. We have previously shown that chemical conjugation of poorly immunogenic TBV antigens to Exoprotein A (EPA) can enhance their immunogenicity. Here, we assessed Outer Membrane Protein Complex (OMPC), a membrane vesicle derived from Neisseria meningitidis, as a carrier for Pfs230. We prepared Pfs230-OMPC conjugates with varying levels of antigen load and examined immunogenicity in mice. Chemical conjugation of Pfs230 to OMPC enhanced immunogenicity and functional activity of the Pfs230 antigen, and OMPC conjugates achieved 2-fold to 20-fold higher antibody titers than Pfs230-EPA/AdjuPhos^® at different doses. OMPC conjugates were highly immunogenic even at low doses, indicating a dose-sparing effect. EPA conjugates induced an IgG subclass profile biased towards a Th2 response, whereas OMPC conjugates induced a strong Th1-biased immune response with high levels of IgG2, which can benefit Pfs230 antibody functional activity, which depends on complement activation. OMPC is a promising carrier for Pfs230 vaccines.

Malaria transmission blocking vaccine: How bacteria can help

Malaria transmission blocking vaccines (TBV) target Plasmodium stages that transmit between human and mosquitos in order to interrupt the parasite’s life cycle and reduce spread. One TBV antigen currently under clinical development is Pf230, which is expressed on sexual Plasmodium stages. In this study, led by Patrick Duffy from the NIAID, researchers improve immunogenicity of Pf230. They chemically conjugate a part of Pf230 to membrane vesicles derived from bacteria, so-called outer membrane protein complexes (OMPC). Immunization of mice with Pf230-OMPC elicits a higher antibody response and a more balanced IgG subclass profile than control immunizations. Serum from Pf230-OMPC-vaccinated mice efficiently blocks infection of mosquitoes. These results with mice encourage further pre-clinical and clinical characterization of OMPC as a carrier for TBV antigens.