|
|
|
|
|
|
|
||
By
From the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore,
Maryland 21205
CD8+ cytotoxic T lymphocytes (CTLs) 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+ CTLs. 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 a more vigorous CD8+ CTL response 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 co-translational translocation into the endoplasmic
reticulum, sensitized target cells expressing this mutant more rapidly for lysis by an env-specific
CTL clone. Additionally, a greatly enhanced de novo env-specific CTL response was induced
in vivo after 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 after 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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
