Effect of the Pre-erythrocytic Candidate Malaria Vaccine RTS,S/AS01(E) on Blood Stage Immunity in Young Children


Bejon, P; Cook, J; Bergmann-Leitner, E; Olotu, A; Lusingu, J; Mwacharo, J; Vekemans, J; Njuguna, P; Leach, A; Lievens, M; Dutta, S; von Seidlein, L; Savarese, B; Villafana, T; Lemnge, MM; Cohen, J; Marsh, K; Corran, PH; Angov, E; Riley, EM; Drakeley, CJ; (2011) Effect of the Pre-erythrocytic Candidate Malaria Vaccine RTS,S/AS01(E) on Blood Stage Immunity in Young Children. The Journal of infectious diseases, 204 (1). pp. 9-18. ISSN 0022-1899 DOI: 10.1093/infdis/jir222

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Abstract

Background. RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection. Methods. We measured, by enzyme-linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01(E) or a control vaccine. Results. Antibody concentrations to AMA-1, EBA-175, and MSP-1(42) decreased with age during the first year of life, then increased to 32 months of age. Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA. Increasing anti-merozoite antibody concentrations and GIA were prospectively associated with increased risk of clinical malaria. Conclusions. Vaccination with RTS,S/AS01(E) reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations. However, in this study, these antibodies were not correlates of clinical immunity to malaria. Instead, heterogeneous exposure led to confounded, positive associations between increasing antibody concentration and increasing risk of clinical malaria.

Item Type: Article
Keywords: plasmodium-falciparum transmission, mozambican children, antibody-responses, growth-inhibition, clinical malaria, febrile, malaria, parasite growth, protection, infection, efficacy, Antibodies, Protozoan, blood, Child, Preschool, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Humans, Infant, Longitudinal Studies, methods, Malaria Vaccines, administration & dosage, immunology, Malaria, Falciparum, epidemiology, immunology, Plasmodium falciparum, growth & development, immunology, Protozoan Proteins, immunology, Risk Factors
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
Vaccine Centre
PubMed ID: 21628653
Web of Science ID: 292561800004
URI: http://researchonline.lshtm.ac.uk/id/eprint/266

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