ASTMH 2016, Caio Martinelle França: “Mosquito Midgut FREP1 is a potential universal malaria transmission-blocking vaccine”

In collaboration with ASTMH, Image Audiovisuals, and session presenters, MESA brings you this webcast from the 65th ASTMH annual meeting in Atlanta, November 2016.

Title: “Mosquito Midgut FREP1 is a potential universal malaria transmission-blocking vaccine”

Speaker: Caio Martinelle França, University of Oklahoma, United States

Session information:  Scientific Session 34: Malaria: Vaccines – Diverse Approaches

Monday, 14 November, 1:45 – 3:30pm, Marriott – Marquis C

Abstract:

Malaria remains a devastating disease. Transmission-blocking vaccines (TBVs) have been recently considered as a promising approach for the elimination and eradication of malaria. We recently discovered a mosquito midgut protein FREP1 that facilitates parasite transmission through direct binding to parasites and it is easily accessible to antibodies co-ingested with blood. Here, we demonstrated that anti-FREP1 antibodies blocked transmission of multiple Plasmodium species (Plasmodium berghei, Plasmodium vivax, and P. falciparum) to multiple Anopheles species (Anopheles gambiae and A. dirus). Sequence comparison of FREP1 orthologs found that a fibrinogen-like (FBG) domain is highly conserved (>90% identity) among Anopheles species from different continents, while the sequence similarity between FBG and human fibrinogens is only about 10%. Immunization of mice with purified recombinant FREP1 shows no significant difference of alanine aminotransferase activity between anti-FREP1 serum and the pre-immune serum. Moreover, the anti-FREP1 serum did not show any cross-reactions with human fibrinogens. Thus, FREP1 is non-toxic or unlikely to cause autoimmune response in mammals. Notably, mice immunized with purified FBG effectively blocked P. berghei transmission (82.1% and 70.1% blockade) to An. gambiae in two independent bioassays respectively. Anti-FREP1 serum from the immunized mice also blocked over 90% infection of P. falciparum in standard membrane-feeding assays (SMFA). In summary, our data support that FREP1 is a promising universal TBV antigen to block the transmission of multiple Plasmodium species to multiple Anopheles species.