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Immunity to Malaria and Vaccine Strategies

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01256

Pfs230 and Pfs48/45 fusion proteins elicit strong transmission-blocking antibody responses against Plasmodium falciparum

 Susheel K Singh1, 2, Susan Thrane1, Bishwanath K. Chourasia1,  Karina Teelen3,  Wouter Graumans3, Rianne Stoter3, Geert-Jan vanGemert3,  Marga G. vandeVegte-Bolmer3, Morten A. Nielsen1, Ali Salanti1, Adam F. Sander3, Robert W. Sauerwein3,  Matthijs M. Jore3* and  Michael Theisen2*
  • 1Department of Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Denmark
  • 2State Serum Institute (SSI), Denmark
  • 3Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Netherlands

The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.

Keywords: Malaria, Multivalent, transmission blocking, Vaccines, Lactococcus lactis

Received: 13 Dec 2018; Accepted: 17 May 2019.

Edited by:

Julius Clemence Hafalla, London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom

Reviewed by:

Rhoel Dinglasan, Emerging Pathogens Institute, University of Florida, United States
Takafumi Tsuboi, Ehime University, Japan  

Copyright: © 2019 Singh, Thrane, Chourasia, Teelen, Graumans, Stoter, vanGemert, vandeVegte-Bolmer, Nielsen, Salanti, Sander, Sauerwein, Jore and Theisen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Matthijs M. Jore, Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, 6525, Netherlands, Matthijs.Jore@radboudumc.nl
Dr. Michael Theisen, State Serum Institute (SSI), Copenhagen, 2300, Hovedstaden, Denmark, mth@ssi.dk