Vaccine Strain-Specificity of Protective HLA-Restricted Class 1 P. falciparum Epitopes

• Published in: PloS one 2016-10, Vol.11 (10), p.e0163026-e0163026
• Main Authors: Sedegah, Martha, Peters, Bjoern, Hollingdale, Michael R, Ganeshan, Harini D, Huang, Jun, Farooq, Fouzia, Belmonte, Maria N, Belmonte, Arnel D, Limbach, Keith J, Diggs, Carter, Soisson, Lorraine, Chuang, Ilin, Villasante, Eileen D
• Format: Article
• Language: English
• Subjects: Acids; Adenoviridae; Adenoviruses; Amino acids; Antigenic determinants; Antigens; Antigens, Protozoan - immunology; Assaying; Biological response modifiers; Biology and Life Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Clinical trials; Comparative analysis; Cytometry; Deoxyribonucleic acid; DNA; Enzyme-linked immunosorbent assay; Epitopes; Epitopes - immunology; Erythrocytes; Flow Cytometry; Histocompatibility antigen HLA; HLA Antigens - immunology; HLA-B Antigens - immunology; Humans; Infections; Interferon; Interferon-gamma - pharmacology; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Malaria; Malaria vaccines; Malaria Vaccines - immunology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Medical research; Medicine; Medicine and Health Sciences; Membrane Proteins - immunology; Military medicine; Peptides; Plasmodium falciparum; Plasmodium falciparum - immunology; Proteins; Protozoan Proteins - immunology; Recall; Research and Analysis Methods; T cell receptors; T cells; T-cell receptor; Vaccines; Vector-borne diseases; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163026

A DNA prime/adenovirus boost malaria vaccine encoding Plasmodium falciparum strain 3D7 CSP and AMA1 elicited sterile clinical protection associated with CD8+ T cell interferon-gamma (IFN-γ) cells responses directed to HLA class 1-restricted AMA1 epitopes of the vaccine strain 3D7. Since a highly effective malaria vaccine must be broadly protective against multiple P. falciparum strains, we compared these AMA1 epitopes of two P. falciparum strains (7G8 and 3D7), which differ by single amino acid substitutions, in their ability to recall CD8+ T cell activities using ELISpot and flow cytometry/intracellular staining assays. The 7G8 variant peptides did not recall 3D7 vaccine-induced CD8+ T IFN-γ cell responses in these assays, suggesting that protection may be limited to the vaccine strain. The predicted MHC binding affinities of the 7G8 variant epitopes were similar to the 3D7 epitopes, suggesting that the amino acid substitutions of the 7G8 variants may have interfered with TCR recognition of the MHC:peptide complex or that the 7G8 variant may have acted as an altered peptide ligand. These results stress the importance of functional assays in defining protective epitopes. Clinical Trials Registrations: NCT00870987, NCT00392015.