title: Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.
abstract: This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related.
authors.affiliation: Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle-upon-Tyne, UK.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Walker
authors.forename: Shinji
authors.initials: S
authors.lastname: Okitsu
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Christopher
authors.initials: C
authors.lastname: Duncan
authors.forename: Mario
authors.initials: M
authors.lastname: Amacker
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.forename: David R
authors.initials: DR
authors.lastname: Cavanagh
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Todryk
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000008:administration & dosage / Q000276:immunology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1
keywords: T cells; antibodies; infectious diseases; malaria