Antibody and T cell responses associated with experimental human malaria infection or vaccination show limited relationships

Walker, Karen, Okitsu, Shinji, Porter, David, Duncan, Christopher, Amacker, Mario, Pluschke, Gerd, Cavanagh, David, Hill, Adrian and Todryk, Stephen (2015) Antibody and T cell responses associated with experimental human malaria infection or vaccination show limited relationships. Immunology, 145 (1). pp. 71-81. ISSN 1365-2567

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Official URL: http://dx.doi.org/10.1111/imm.12428

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 5 bites of Plasmodium falciparum-infected mosquitos, with individuals reaching patent infection by 11-12 days, having harboured 4-5 blood stage cycles prior to 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 IFNγ and IL-4 ELIspot, but their magnitude did not correlate with 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 IFNγ, 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.

Item Type: Article
Uncontrolled Keywords: antibodies, infectious diseases, malaria, T cells
Subjects: C500 Microbiology
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Nicola King
Date Deposited: 17 Mar 2015 16:09
Last Modified: 21 Sep 2015 13:12
URI: http://nrl.northumbria.ac.uk/id/eprint/18458

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