A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120.
Peptide-based vaccines that directly target T cell or B cell epitopes may have significant advantages over conventional vaccines. Further, synthetic chimeric peptides that combine strong T cell epitopes with poorly immunogenic, but immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful in eliciting antibody to such important regions. Here we characterize a human T cell epitope analyzed in 54 individuals immunized with a hepatitis B virus surface Ag vaccine. Primary cultures from a total of 59 immunized donors were assessed for their ability to respond to hepatitis B virus surface Ag and peptides, and five were non-responders (8.5%). T cell lines were established from the remaining 54 responders. Of the responders, it was found that the peptide representing amino acids 19 through 33 (19-33) elicited significant proliferation in lines derived from 50 donors. This "universal" T cell epitope, which was recognized in donors of many different HLA-DR and -DQ haplotypes, was then used to construct a chimeric peptide containing 19-33 and the third V region loop structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune response to the V3 loop peptide. The V3 loop is the region to which significant neutralizing antibody is directed. Thus, a strong immune response to a synthetic peptide that contains the strain-conserved V3 loop region could have significant therapeutic implications. The V3 loop/19-33 peptide was then used to prime mice, to determine whether V3 loop-specific antibody could be induced. The peptide elicited potent 19-33-specific proliferation in T cells isolated from draining lymph nodes, and in six of six mice anti-V3 loop antibody was elicited. Further, V3 loop/19-33-primed animals made significant levels of antibody that bound rgp120. These data suggest that, when a major T cell epitope is synthesized in tandem with the V3 loop, a significant immune response against the loop can be elicited. Thus, given the finding that neutralizing antibody may play a role in the control and/or prevention of HIV infection, an HIV vaccine composed of a T cell epitope-containing peptide may prove effective. In addition, this type of approach can be generalized to the design of peptide-based vaccines.
Greenstein
J L
JL
ImmuLogic Pharmaceutical Corporation, Cambridge, MA 02139.
Schad
V C
VC
Goodwin
W H
WH
Brauer
A B
AB
Bollinger
B K
BK
Chin
R D
RD
Kuo
M C
MC
D000595:Amino Acid Sequence; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D006514:Hepatitis B Surface Antigens; D010455:Peptides