Format

Send to

Choose Destination
See comment in PubMed Commons below
Malar J. 2016 Feb 1;15:55. doi: 10.1186/s12936-016-1098-8.

Measurement of ex vivo ELISpot interferon-gamma recall responses to Plasmodium falciparum AMA1 and CSP in Ghanaian adults with natural exposure to malaria.

Author information

  • 1Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. harini.d.ganeshan.ctr@mail.mil.
  • 2Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. akusi@noguchi.ug.edu.gh.
  • 3Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. danum@noguchi.ug.edu.gh.
  • 4Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. michael.hollingdale.ctr@mail.mil.
  • 5La Jolla Institute for Allergy and Immunology, La Jolla, San Diego, CA, USA. bpeters@liai.org.
  • 6La Jolla Institute for Allergy and Immunology, La Jolla, San Diego, CA, USA. ykim@liai.org.
  • 7Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. jtetteh@noguchi.ug.edu.gh.
  • 8Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. mofori@noguchi.ug.edu.gh.
  • 9Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. bgyan@noguchi.ug.edu.gh.
  • 10Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. kkoram@noguchi.ug.edu.gh.
  • 11Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. jun.huang.ctr@mail.mil.
  • 12Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. maria.n.belmonte.ctr@mail.mil.
  • 13Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. joglenna.g.banania.ctr@mail.mil.
  • 14Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. ddodoo@noguchi.ug.edu.gh.
  • 15Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. eileen.d.villasante.civ@mail.mil.
  • 16Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. martha.sedegah.civ@mail.mil.

Abstract

BACKGROUND:

Malaria eradication requires a concerted approach involving all available control tools, and an effective vaccine would complement these efforts. An effective malaria vaccine should be able to induce protective immune responses in a genetically diverse population. Identification of immunodominant T cell epitopes will assist in determining if candidate vaccines will be immunogenic in malaria-endemic areas. This study therefore investigated whether class I-restricted T cell epitopes of two leading malaria vaccine antigens, Plasmodium falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1), could recall T cell interferon-γ responses from naturally exposed subjects using ex vivo ELISpot assays.

METHODS:

Thirty-five subjects aged between 24 and 43 years were recruited from a malaria-endemic urban community of Ghana in 2011, and their peripheral blood mononuclear cells (PBMCs) were tested in ELISpot IFN-γ assays against overlapping 15mer peptide pools spanning the entire CSP and AMA1 antigens, and 9-10mer peptide epitope mixtures that included previously identified and/or predicted human leukocyte antigen (HLA) class 1-restricted epitopes from same two antigens.

RESULTS:

For CSP, 26 % of subjects responded to at least one of the nine 15mer peptide pools whilst 17 % responded to at least one of the five 9-10mer HLA-restricted epitope mixtures. For AMA1, 63 % of subjects responded to at least one of the 12 AMA1 15mer peptide pools and 51 % responded to at least one of the six 9-10mer HLA-restricted epitope mixtures. Following analysis of data from the two sets of peptide pools, along with bioinformatics predictions of class I-restricted epitopes and the HLA supertypes expressed by a subset of study subjects, peptide pools that may contain epitopes recognized by multiple HLA supertypes were identified. Collectively, these results suggest that natural transmission elicits ELISpot IFN-γ activities to class 1-restricted epitopes that are largely HLA-promiscuous.

CONCLUSIONS:

These results generally demonstrate that CSP and AMA1 peptides recalled ELISpot IFN-γ responses from naturally exposed individuals and that both CSP and AMA1 contain diverse class 1-restricted epitopes that are HLA-promiscuous and are widely recognized in this population.

PMID:
26830334
PMCID:
PMC4736649
DOI:
10.1186/s12936-016-1098-8
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center