Targeting of HIV-1 antigens for rapid intracellular degradation enhances CTL recognition and the induction of de novo CTL responses in vivo following immunization.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Targeting of HIV-1 antigens for rapid intracellular degradation enhances CTL recognition and the induction of de novo CTL responses in vivo following immunization.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:62. Unique Identifier : AIDSLINE MED/97927042
Tobery TO; Siliciano RF; Johns Hopkins University School of Medicine, Baltimore, MD. Fax: 410); 955-0964.

Abstract: CD8+ CTL have the ability to recognize and eliminate virally infected cells before new virions are produced within that cell. Therefore, a rapid and vigorous CD8+ CTL response, induced by vaccination, can, in principle, prevent disseminated infection in vaccinated individuals who are exposed to the relevant virus. There has thus been interest in novel vaccine strategies that will enhance the induction of CD8+ CTL. In this study, we have tested the hypothesis that targeting an antigen to undergo more efficient processing by the Class I processing pathway will elicit more vigorous CD8+ CTL against that antigen. Targeting a type I transmembrane protein, the HIV-1 envelope (env) protein, for expression in the cytoplasm, rather than allowing its normal cotranslational translocation into the endoplasmic reticulum, sensitized target cells expressing this mutant to much more rapid lysis by an env-specific CTL clone. Additionally, a greatly enhanced de novo env-specific CTL response was induced in vivo following immunization of mice with recombinant vaccinia vectors expressing the cytoplasmic env mutant. Similarly, targeting a cytoplasmic protein, HIV-1 nef, to undergo rapid cytoplasmic degradation induced a greatly enhanced de novo nef-specific CD8+ CTL response in vivo following immunization of mice with either recombinant vaccinia vectors or DNA expression plasmids expressing the degradation targeted nef mutant. The targeting of viral antigens for rapid cytoplasmic degradation represents a novel and highly effective vaccine strategy for the induction of enhanced de novo CTL responses in vivo.

Keywords: *CD8-Positive T-Lymphocytes/IMMUNOLOGY *HIV Antigens/IMMUNOLOGY *HIV-1/IMMUNOLOGY *T-Lymphocytes, Cytotoxic/IMMUNOLOGY
971130
M97B1181

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