Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Sustainable Development Goals
03 Saúde e Bem-EstarCollections
- IOC - Artigos de Periódicos [12973]
Metadata
Show full item record
VACCINATION WITH GAG, VIF, AND NEF GENE FRAGMENTS AFFORDS PARTIAL CONTROL OF VIRAL REPLICATION AFTER MUCOSAL CHALLENGE WITH SIVMAC239
HIV
Vaccination regimens
T-cell responses
Author
Affilliation
Abstract
Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency
viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential
targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant
and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among
several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with “minigenes” encoding fragments
of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication.Wedelivered these minigenes
through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along
with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant
adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced
T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation
of immunodominance. Indeed, Mamu-A*01 vaccinees mounted CD8 T cells directed against only one subdominant epitope,
regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set
point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell
responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication.
Keywords in Portuguese
HIVKeywords
Human and simian immunodeficiency viruses (HIV and SIV)HIV
Vaccination regimens
T-cell responses
Share