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Communication

Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope

1
School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada
2
Institute for Glycomics, Griffith University, Southport, Queensland 4215, Australia
3
Department of Medical Microbiology & Immunology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(3), 392; https://doi.org/10.3390/vaccines8030392
Received: 26 May 2020 / Revised: 28 June 2020 / Accepted: 10 July 2020 / Published: 18 July 2020
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
In pregnant women, Plasmodium falciparum-infected red blood cells adhere to the placenta via the parasite protein VAR2CSA. Two vaccine candidates based on VAR2CSA are currently in clinical trials; however, these candidates failed to elicit strain-transcending antibody responses. We previously showed that a cross-reactive monoclonal antibody (3D10) raised against the P. vivax antigen PvDBP targets epitopes in VAR2CSA. We now aim to design a peptide vaccine against VAR2CSA based on the epitope that generated 3D10. We mapped the epitope to subdomain 1 (SD1) of PvDBP and identified a peptide that contained the minimal sequence. However, this peptide did not elicit cross-reactive VAR2CSA antibodies in mice. When tested against a broader, overlapping peptide array spanning SD1, 3D10 in fact recognized a discontinuous epitope consisting of three segments of SD1. These findings presented the challenge to generate this larger structural epitope as a synthetic peptide since it is stabilized by two pairs of disulfide bonds. We overcame this using a synthetic scaffold to conformationally constrain the SD1 peptide and coupled it to keyhole limpet hemocyanin (KLH). The SD1-KLH conjugate elicited antibodies in mice that cross-reacted with VAR2CSA. This strategy successfully recapitulated a discontinuous epitope with a synthetic peptide and represents the first heterologous vaccine candidate against VAR2CSA. View Full-Text
Keywords: Plasmodium falciparum; Plasmodium vivax; vaccine; placental malaria; peptide; PvDBP; VAR2CSA Plasmodium falciparum; Plasmodium vivax; vaccine; placental malaria; peptide; PvDBP; VAR2CSA
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MDPI and ACS Style

Mitran, C.J.; Higa, L.M.; Good, M.F.; Yanow, S.K. Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope. Vaccines 2020, 8, 392. https://doi.org/10.3390/vaccines8030392

AMA Style

Mitran CJ, Higa LM, Good MF, Yanow SK. Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope. Vaccines. 2020; 8(3):392. https://doi.org/10.3390/vaccines8030392

Chicago/Turabian Style

Mitran, Catherine J., Lauren M. Higa, Michael F. Good, and Stephanie K. Yanow. 2020. "Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope" Vaccines 8, no. 3: 392. https://doi.org/10.3390/vaccines8030392

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