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

Lookup NU author(s): Dr Christopher Duncan, Dr Stephen Todryk

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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.


Publication metadata

Author(s): Walker KM, Okitsu S, Porter DW, Duncan C, Amacker M, Pluschke G, Cavanagh DR, Hill AV, Todryk SM

Publication type: Article

Publication status: Published

Journal: Immunology

Year: 2014

Volume: 145

Issue: 1

Pages: 71-81

Print publication date: 07/04/2015

Online publication date: 03/12/2014

Acceptance date: 21/11/2014

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Wiley-Blackwell Publishing Ltd.

URL: https://doi.org/10.1111/imm.12428

DOI: 10.1111/imm.12428

PubMed id: 25471322


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