Immunodominant T cell peptides from four candidate malarial antigens as biomarkers of protective immunity against malaria

• Published in: Vaccine Vol. 41; no. 6; pp. 1265 - 1273
• Main Authors: Belmonte, Maria, Ganeshan, Harini, Huang, Jun, Belmonte, Arnel, Inoue, Sandra, Velasco, Rachel, Acheampong, Neda, Ofori, Ebenezer Addo, Akyea-Mensah, Kwadwo, Frimpong, Augustina, Ennuson, Nana Aba, Frempong, Abena Fremaah, Kyei-Baafour, Eric, Amoah, Linda Eva, Edgel, Kimberly, Peters, Bjoern, Villasante, Eileen, Kusi, Kwadwo Asamoah, Sedegah, Martha
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 03-02-2023; Elsevier Limited
• Subjects: Adult; Antigens; Antigens, Protozoan; Apical membrane antigen 1; Biomarkers; CD8 antigen; Circumsporozoite protein; Cryopreservation; Disease control; Epitope; Epitopes; Epitopes, T-Lymphocyte; FluoroSpot; Granzyme B; Granzymes; Hepatitis; Histocompatibility antigen HLA; Human subjects; Humans; IFN-γ; Immunity; Immunodominance; Leukocytes, Mononuclear; Lymphocytes; Lymphocytes T; Malaria; Malaria Vaccines; Medical research; Membrane proteins; Parasites; Peptides; Peripheral blood mononuclear cells; Plasmodium falciparum; Pools; Population genetics; Populations; Proteins; Protozoan Proteins; R&D; Research & development; Sporozoites; T cells; Thrombospondin; Vaccines; Vector-borne diseases; Zygotes; γ-Interferon; United States > US; Ghana; NMIMR; CSP; FluoroSpot; AMA1; TCR; Malaria; Epitope; MHC; TRAP; T cells; PBMC; IFN-γ; Granzyme B; NMRC; CelTOS; HLA; WHO
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2023.01.016

•135 T cell epitopes identified in four P. falciparum antigen, with 75 % being novel.•Thirty-two percent (32%) of the 135 epitopes show promiscuity in HLA binding.•Fifty-two percent (52%) are conserved across 16 highly diverse parasite variants.•CSP and AMA1 had greater numbers of T cell epitopes compared to TRAP and CelTOS.
A malaria vaccine with high efficacy and capable of inducing sterile immunity against malaria within genetically diverse populations is urgently needed to complement ongoing disease control and elimination efforts. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection and the rapid identification of malaria antigen targets that elicit these responses will fast-track the development of simpler, cost-effective interventions. This study extends our previous work which used peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites to identify immunodominant antigen-specific peptide pools composed of overlapping 15mer sequences spanning full length proteins of four malarial antigens. Our current study aimed to identify CD8 + T cell epitopes within these previously identified positive peptide pools. Cryopreserved PBMCs from 109 HLA-typed subjects were stimulated with predicted 9-11mer CD8 + T cell epitopes from P. falciparum circumsporozoite protein (CSP), apical membrane antigen 1 (AMA1), thrombospondin related anonymous protein (TRAP) and cell traversal for ookinetes and sporozoites (CelTOS) in FluoroSpot assays. A total of 135 epitopes out of 297 tested peptides from the four antigens were experimentally identified as positive for IFN-γ and/or granzyme B production in 65 of the 109 subjects. Forty-three of 135 epitopes (32 %) were promiscuous for HLA binding, with 31 of these promiscuous epitopes (72 %) being presented by HLA alleles that fall within at least two different HLA supertypes. Furthermore, about 52 % of identified epitopes were conserved when the respective sequences were aligned with those from 16 highly diverse P. falciparum parasite strains. In summary, we have identified a number of conserved epitopes, immune responses to which could be effective against multiple P. falciparum parasite strains in genetically diverse populations.