Characterization of Plasmodium berghei PbP47 as a Malaria Transmission Blocking Vaccine Target

Authors

• L Yenkoidiok Douti
• GE Canepa
• C Barillas-Mury

Abstract

Malaria is an infectious disease caused by Plasmodium parasites and transmitted through the bite of an infected female Anopheles mosquito. Reducing malaria transmission is central to control and ultimately eradicate the disease. Recent studies suggest that antibodies directed against Plasmodium proteins expressed in the mosquito stages could inhibit parasite development; however, only a few vaccine candidates induced compelling transmission-blocking activities. Recently, our lab characterized Pfs47, a protein localized on the surface of several mosquito-stages of the parasite (gametes, zygotes and ookinetes), and shown that anti-Pfs47 antibodies effectively block malaria transmission. Here, we used Pbs47, an ortholog of Pfs47 in Plasmodium berghei, to access the in vivo efficacy of a P47 vaccine. Pbs47 was expressed as E. coli recombinant protein and used to immunize mice following a prime/boost vaccination regimen along with CpG adjuvant. Sera was collected on days 21 and 42 to assess the intensity and specificity of antibody responses by ELISA. Immunized and control mice were infected with P. berghei parasites on day 42, and mosquitoes were challenged on the mice to evaluate vaccine efficacy. Results indicate that immunization induce 45% reduction in parasite density in Anopheles gambiae mosquito. Interestingly, purified antibodies from immunized mice, when passively transferred to immunologically naïve mice infected with P. berghei, reduced parasite load in the mosquito by 80%. These data demonstrate that antibody to Pbs47 can be protective; however, fine-tuning the vaccine formulation or optimizing the vaccine delivery system would be required to achieve a stronger transmission-blocking response.

Scientific Focus Area: Microbiology and Infectious Diseases

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