Vaccine Strain-Specificity of Protective HLA-Restricted Class 1 P. falciparum Epitopes.
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.
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Martha
M
Sedegah
La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, United States of America.
Bjoern
B
Peters
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Michael R
http://orcid.org/0000-0002-2343-3824
MR
Hollingdale
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Harini D
HD
Ganeshan
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Jun
J
Huang
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Fouzia
F
Farooq
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Maria N
MN
Belmonte
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Arnel D
AD
Belmonte
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, 20817, United States of America.
Keith J
KJ
Limbach
USAID, Washington, DC, 20523, United States of America.
Carter
C
Diggs
USAID, Washington, DC, 20523, United States of America.
Lorraine
L
Soisson
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Ilin
I
Chuang
Malaria Department, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Eileen D
ED
Villasante
D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008565:Membrane Proteins / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology
D000953:Antigens, Protozoan; D000939:Epitopes; D006680:HLA Antigens; D015235:HLA-B Antigens; C562005:HLA-B58; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D007371:Interferon-gamma
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