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: Karen M Walker, Shinji Okitsu, David W Porter, Christopher Duncan, Mario Amacker, Gerd Pluschke, David R Cavanagh, Adrian V S Hill, Stephen M Todryk
• Journal: Immunology (Immunology) Vol. 145 Issue 1 Pg. 71-81 (May 2015) ISSN: 1365-2567 [Electronic] England
• PMID: 25471322 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Protozoan
• Cytokines
• Immunoglobulin G
• Immunoglobulin M
• Malaria Vaccines
• Merozoite Surface Protein 1

Topics

• Adolescent
• Adult
• Antibodies, Protozoan (immunology)
• Antibody Formation (drug effects)
• Cytokines (immunology)
• Female
• Humans
• Immunity, Cellular (drug effects)
• Immunoglobulin G (immunology)
• Immunoglobulin M (immunology)
• Malaria Vaccines (administration & dosage, immunology)
• Malaria, Falciparum (immunology, pathology, prevention & control)
• Male
• Merozoite Surface Protein 1 (administration & dosage, immunology)
• Middle Aged
• Plasmodium falciparum (immunology)
• T-Lymphocytes (immunology)