Measuring naturally acquired immune responses to candidate malaria vaccine antigens in Ghanaian adults

Dodoo, Daniel, Hollingdale, Michael R., Anum, Dorothy, Koram, Kwadwo A., Gyan, Ben, Akanmori, Bartholomew D., Ocran, Josephine, Adu-Amankwah, Susan, Geneshan, Harini, Abot, Esteban, Legano, Jennylyn, Banania, Glenna, Sayo, Renato, Brambilla, Donald, Kumar, Sanjai, Doolan, Denise L., Rogers, William O., Epstein, Judith, Richie, Thomas L., and Sedegah, Martha (2011) Measuring naturally acquired immune responses to candidate malaria vaccine antigens in Ghanaian adults. Malaria Journal, 10 (168). pp. 1-18.

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Abstract

Background: To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens. Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays.

Methods: In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA. Positive ELISA responses were determined using two methods. T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-γ ELISpot assays using HLA-matched Class I- and DR-restricted synthetic peptides. In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart.

Results: In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses. ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities. DR-restricted peptides showed stronger responses than Class I-restricted peptides. In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated. Results varied significantly between the two-week time-points for many participants.

Conclusions: All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity. Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated. However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals.

Item ID: 41445
Item Type: Article (Research - C1)
ISSN: 1475-2875
Additional Information:

© Dodoo et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: Naval Medical Research Centre (NMRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
Projects and Grants: NMRC 6000.RAD1.F.A0309, NIAID/NIH contract NO1 AI95363.
Date Deposited: 24 Mar 2016 02:00
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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