title: Acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria.
abstract: BACKGROUND
  Malaria still represents a major cause of morbidity and mortality predominantly in several developing countries, and remains a priority in many public health programmes. Despite the enormous gains made in control and prevention the development of an effective vaccine represents a persisting challenge. Although several parasite antigens including pre-erythrocytic antigens and blood stage antigens have been thoroughly investigated, the identification of solid immune correlates of protection against infection by Plasmodium falciparum or clinical malaria remains a major hurdle. In this study, an immuno-epidemiological survey was carried out between two populations naturally exposed to P. falciparum malaria to determine the immune correlates of protection.
  
  
  METHODS
  Plasma samples of immune adults from two countries (Ghana and Madagascar) were tested for their reactivity against the merozoite surface proteins MSP1-19, MSP3 and AMA1 by ELISA. The antigens had been selected on the basis of cumulative evidence of their role in anti-malarial immunity. Additionally, reactivity against crude P. falciparum lysate was investigated. Purified IgG from these samples were furthermore tested in an invasion inhibition assay for their antiparasitic activity.
  
  
  RESULTS
  Significant intra- and inter- population variation of the reactivity of the samples to the tested antigens were found, as well as a significant positive correlation between MSP1-19 reactivity and invasion inhibition (p < 0.05). Interestingly, male donors showed a significantly higher antibody response to all tested antigens than their female counterparts. In vitro invasion inhibition assays comparing the purified antibodies from the donors from Ghana and Madagascar did not show any statistically significant difference. Although in vitro invasion inhibition increased with breadth of antibody response, the increase was not statistically significant.
  
  
  CONCLUSIONS
  The findings support the fact that the development of semi-immunity to malaria is probably contingent on the development of antibodies to not only one, but a range of antigens and that invasion inhibition in immune adults may be a function of antibodies to various antigens. This supports strategies of vaccination including multicomponent vaccines as well as passive vaccination strategies with antibody cocktails.
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. oaddai-mensah.chs@knust.edu.gh.|RWTH Aachen University, Institute for Molecular Biotechnology, Worringerweg 1, 52074, Aachen, Germany. oaddai-mensah.chs@knust.edu.gh.|Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. oaddai-mensah.chs@knust.edu.gh.
authors: Otchere
authors: O
authors: Addai-Mensah
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. melanie.seidel@ime.fraunhofer.de.
authors: Melanie
authors: M
authors: Seidel
authors: Department of Biomedical Laboratory Science, School of Medicine and Health Science, University for Development Studies, Tamale, Ghana. nafamidu@yahoo.com.
authors: Nafiu
authors: N
authors: Amidu
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. dominika.maskus@rwth-aachen.de.
authors: Dominika J
authors: DJ
authors: Maskus
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. stephanie.kapelski@rwth-aachen.de.
authors: Stephanie
authors: S
authors: Kapelski
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. gudrun.breuer@ime.fraunhofer.de.
authors: Gudrun
authors: G
authors: Breuer
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. carmen.franken@ime.fraunhofer.de.
authors: Carmen
authors: C
authors: Franken
authors: Kumasi Centre for Collaborative Research, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. owusudabo@kccr.de.
authors: Ellis
authors: E
authors: Owusu-Dabo
authors: Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. mtfrempong@gmail.com.
authors: Margaret
authors: M
authors: Frempong
authors: Laboratoire de Microbiologie et de Parasitologie, ESSAGRO-Faculté de Médecine, Université d'Antananarivo, Antananarivo, Madagascar. rakrapha13@gmail.com.
authors: Raphaël
authors: R
authors: Rakotozandrindrainy
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. helga.schinkel@ime.fraunhofer.de.
authors: Helga
authors: H
authors: Schinkel
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. andreas.reimann@ime.fraunhofer.de.
authors: Andreas
authors: A
authors: Reimann
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. torsten.klockenbring@ime.fraunhofer.de.
authors: Torsten
authors: T
authors: Klockenbring
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. stefan.barth@uct.ac.za.|Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering at RWTH Aachen University and Hospital, Pauwelsstraße 20, 52074, Aachen, Germany. stefan.barth@uct.ac.za.|South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, South Africa. stefan.barth@uct.ac.za.
authors: Stefan
authors: S
authors: Barth
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. rainer.fischer@ime.fraunhofer.de.|RWTH Aachen University, Institute for Molecular Biotechnology, Worringerweg 1, 52074, Aachen, Germany. rainer.fischer@ime.fraunhofer.de.
authors: Rainer
authors: R
authors: Fischer
authors: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074, Aachen, Germany. rolf.fendel@ime.fraunhofer.de.|RWTH Aachen University, Institute for Molecular Biotechnology, Worringerweg 1, 52074, Aachen, Germany. rolf.fendel@ime.fraunhofer.de.|Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering at RWTH Aachen University and Hospital, Pauwelsstraße 20, 52074, Aachen, Germany. rolf.fendel@ime.fraunhofer.de.
authors: Rolf
authors: R
authors: Fendel
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins