Peptide immunization in humans: a combined CD8+/CD4+ T cell-targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL).

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Peptide immunization in humans: a combined CD8+/CD4+ T cell-targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL).

Clin Exp Immunol. 1996 Jul;105(1):18-25. Unique Identifier : AIDSLINE MED/96280772
Brander C; Corradin G; Hasler T; Pichler WJ; Institute of Immunology and Allergology, Inselspital, Bern,; Switzerland.

Abstract: Immunization with short antigenic peptides represents a potential strategy to induce peptide-specific CTL in vivo. In this study, a synthetic vaccine consisting of an HIV-derived, HLA-A2.1-binding CTL epitope and a tetanus toxin-derived T helper epitope was evaluated for its capacity to induce peptide-specific CTL in humans. Thirteen volunteers were immunized and boosted twice with 100 micrograms of the CTL epitope plus 300 micrograms of the T helper peptide (p30). Peripheral blood mononuclear cells (PBMC) were regularly analysed for cytotoxic and proliferative responses before, between and after the immunizations, and the serum was tested for anti-peptide antibodies. No unequivocal induction of HIV peptide-specific CTL in any of the volunteers was observed. However, a wide pattern of mild and transient side reactions was observed, ranging from local redness at the injection site to generalized exanthema, myalgias, arthralgias and fever. The side-effects were related to the T helper epitope, as they were similar to the side-effects experienced after tetanus immunization, correlated to the magnitude of the p30-specific in vitro proliferative response, and occurred only if p30 was co-injected. No antibodies against the HIV-derived peptides nor against p30 were detectable in the serum after repeated immunizations. The data suggest that the CTL peptide, at the concentration used in this study, failed to induce a cytotoxic immune response in vivo, although the T helper peptide seems to be capable of restimulating the specific memory T cells.

Keywords: Adult Amino Acid Sequence AIDS Vaccines/ADVERSE EFFECTS/*IMMUNOLOGY/*PHARMACOLOGY CD4-Positive T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Epitopes/IMMUNOLOGY Female Human Immunologic Memory/*DRUG EFFECTS Injections, Subcutaneous/ADVERSE EFFECTS Lymphocyte Transformation/*DRUG EFFECTS Male Middle Age Molecular Sequence Data Peptides/ADVERSE EFFECTS/*IMMUNOLOGY/*PHARMACOLOGY Support, Non-U.S. Gov't T-Lymphocytes, Cytotoxic/DRUG EFFECTS/*IMMUNOLOGY CLINICAL TRIAL JOURNAL ARTICLE
961130
M96B1845

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