Cell-mediated immune responses to vaccine peptides derived from the circumsporozoite protein of Plasmodium falciparum.
T cell epitopes residing within vaccine candidate peptides have been identified by delayed-type hypersensitivity (DTH) responses in mice. The recombinant sporozoite vaccine candidate, R32tet32, contains at least two T epitopes, one located within the repeat region and another in the tet tail. When C57BL/6 (H-2b) and BALB/c (H-2d) mice were sensitized intradermally with R32tet32 or the truncated protein R32LR emulsified in CFA and challenged 5 days later with R32tet32, only H-2b mice recognized a T epitope located within the major repeat sequence (NANP) and encoded by four or less repeats. H-2d mice responded solely to the T epitope located on the tet tail. Ear swelling was maximal at 48 h and revealed a histologic pattern characteristic of DTH. CD4+ T cell lines derived from immunized animals demonstrated the ability to mediate local DTH, proliferate, and secrete lymphokines in response to stimulation with Ag. High dose i.v. administration of R32tet32 in C57BL/6 and BALB/c mice before intradermal sensitization with R32tet32 revealed that DTH responses were suppressed only in BALB/c mice. Further experiments localized the suppressive determinant to the tet tail. Collectively, these data indicate that DTH may prove to be a useful method to characterize the biologic activity of T epitopes, furthermore they suggest that candidate vaccine peptides should be tested for suppressive activity before inclusion in a vaccine.
Russo
D M
DM
Department of Microbiology and Immunology, Hahnemann University, Philadelphia, PA 19102.
Sundy
J S
JS
Young
J F
JF
Maguire
H C
HC
Weidanz
W P
WP
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001386:Azides / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D010449:Peptide Mapping; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D001386:Azides; D000939:Epitopes; D006183:H-2 Antigens; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015800:Protozoan Proteins; D014612:Vaccines; C041595:circumsporozoite protein, Protozoan; D011732:Pyridoxal Phosphate; C044823:N-4-azido-2-nitrophenylpyridoxyl-5-phosphate