Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge

PLoS One. 2015 Jul 6;10(7):e0131456. doi: 10.1371/journal.pone.0131456. eCollection 2015.

Abstract

Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood*
  • Immunization
  • Malaria Vaccines / therapeutic use*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Plasmodium falciparum / immunology*
  • Rabbits

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines

Grants and funding

This work was supported by the Fraunhofer Zukunftsstiftung (http://www.fraunhofer.de/). SK was supported by a "Richtlinien zur Förderung des wissenschaftlichen Nachwuchses (RFwN) Ph.D. grant" from Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University (http://www.rwth-aachen.de/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. TropIQ Health Sciences provided support in the form of salaries for authors JMB, KLD and RWS but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.