PMID- 26830334 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1475-2875 (Electronic) IS - 1475-2875 (Linking) VI - 15 DP - 2016 Feb 1 TI - Measurement of ex vivo ELISpot interferon-gamma recall responses to Plasmodium falciparum AMA1 and CSP in Ghanaian adults with natural exposure to malaria. PG - 55 LID - 10.1186/s12936-016-1098-8 [doi] LID - 55 AB - 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-gamma 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-gamma 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-gamma activities to class 1-restricted epitopes that are largely HLA-promiscuous. CONCLUSIONS: These results generally demonstrate that CSP and AMA1 peptides recalled ELISpot IFN-gamma 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. FAU - Ganeshan, Harini AU - Ganeshan H AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. harini.d.ganeshan.ctr@mail.mil. FAU - Kusi, Kwadwo A AU - Kusi KA AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. akusi@noguchi.ug.edu.gh. FAU - Anum, Dorothy AU - Anum D AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. danum@noguchi.ug.edu.gh. FAU - Hollingdale, Michael R AU - Hollingdale MR AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. michael.hollingdale.ctr@mail.mil. FAU - Peters, Bjoern AU - Peters B AD - La Jolla Institute for Allergy and Immunology, La Jolla, San Diego, CA, USA. bpeters@liai.org. FAU - Kim, Yohan AU - Kim Y AD - La Jolla Institute for Allergy and Immunology, La Jolla, San Diego, CA, USA. ykim@liai.org. FAU - Tetteh, John K A AU - Tetteh JK AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. jtetteh@noguchi.ug.edu.gh. FAU - Ofori, Michael F AU - Ofori MF AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. mofori@noguchi.ug.edu.gh. FAU - Gyan, Ben A AU - Gyan BA AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. bgyan@noguchi.ug.edu.gh. FAU - Koram, Kwadwo A AU - Koram KA AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. kkoram@noguchi.ug.edu.gh. FAU - Huang, Jun AU - Huang J AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. jun.huang.ctr@mail.mil. FAU - Belmonte, Maria AU - Belmonte M AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. maria.n.belmonte.ctr@mail.mil. FAU - Banania, Jo Glenna AU - Banania JG AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. joglenna.g.banania.ctr@mail.mil. FAU - Dodoo, Daniel AU - Dodoo D AD - Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. ddodoo@noguchi.ug.edu.gh. FAU - Villasante, Eileen AU - Villasante E AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. eileen.d.villasante.civ@mail.mil. FAU - Sedegah, Martha AU - Sedegah M AD - Malaria Department, Naval Medical Research Center, Silver Spring, MD, USA. martha.sedegah.civ@mail.mil. LA - eng GR - N01 AI95363/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160201 PL - England TA - Malar J JT - Malaria journal JID - 101139802 RN - 0 (Protozoan Proteins) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Computational Biology MH - Enzyme-Linked Immunospot Assay MH - Female MH - Humans MH - Interferon-gamma/*metabolism MH - Malaria/*immunology/*metabolism MH - Male MH - Plasmodium falciparum/*immunology MH - Protozoan Proteins/*immunology MH - Young Adult PMC - PMC4736649 EDAT- 2016/02/03 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/02/01 CRDT- 2016/02/03 06:00 PHST- 2015/10/17 00:00 [received] PHST- 2016/01/12 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - 10.1186/s12936-016-1098-8 [pii] AID - 1098 [pii] AID - 10.1186/s12936-016-1098-8 [doi] PST - epublish SO - Malar J. 2016 Feb 1;15:55. doi: 10.1186/s12936-016-1098-8.