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

Karen Walker, Shinji Okitsu, David Porter, Christopher Duncan, Mario Amacker, Gerd Pluschke, David Cavanagh, Adrian Hill, Stephen Todryk

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)71-81
JournalImmunology
Volume145
Issue number1
DOIs
Publication statusPublished - May 2015

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