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

Autor:	Scaria PV; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Rowe CG; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Chen BB; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Muratova OV; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Fischer ER; 2Rocky Mountain Laboratory, NIAID/NIH, Hamilton, MT 59840 USA., Barnafo EK; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Anderson CF; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Zaidi IU; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Lambert LE; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Lucas BJ; 3Merck & Co., Inc, Kenilworth, NJ USA., Nahas DD; 3Merck & Co., Inc, Kenilworth, NJ USA., Narum DL; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA., Duffy PE; 1Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD 20892 USA.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2019 Jul 08; Vol. 4, pp. 24. Date of Electronic Publication: 2019 Jul 08 (Print Publication: 2019).
DOI:	10.1038/s41541-019-0121-9
Abstrakt:	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. Competing Interests: Competing interestsB.J.L. and D.D.N. are employed by Merck & Co., Inc., Kenilworth, NJ, USA. The remaining authors declare no competing interests.
Databáze:	MEDLINE
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