Self heat-shock protein (hsp60) peptide serves in a conjugate vaccine against a lethal pneumococcal infection.
Healthy persons manifest a high frequency of T cells reactive to epitopes of the self 60-kDa heat-shock protein (hsp60) molecule. It was reasoned that a self hsp60 peptide, p458m, might provide T cell help for a response to the T independent capsular polysaccharide of Streptococcus pneumoniae type 4 (PS4). The conjugate vaccine (PS4-p458m) induced resistance to challenge with >300,000 times the minimal lethal dose of pneumococci. PS4 conjugated to other immunogenic carriers (tetanus toxoid, a pneumolysin peptide, and others) or a commercial pneumococcal vaccine were far less effective. The effectiveness of the PS4-p458m conjugate was associated with an increased IgG1 antibody response to PS4, with long-term memory, and with T cell responses to the p458m peptide. Thus, T cell reactivity to a self epitope in a conjugate vaccine can be mobilized to induce help for resistance to a lethal infection.
Könen-Waisman
S
S
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Cohen
A
A
Fridkin
M
M
Cohen
I R
IR
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018834:Chaperonin 60 / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage
D001428:Bacterial Vaccines; D018834:Chaperonin 60; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C053136:pneumonococcal polysaccharide, type 4