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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
Autor
Martins, Mauricio A.
Wilson, Nancy A.
Plaskowski, Shari M.
Weisgrau, Kim L.
Furlott, Jessica R.
Bonaldo, Myrna C.
Santana, Marlon G. Veloso de
Rudersdorf, Richard A.
Rakasz, Eva G.
Keating, Karen D.
Chiuchiolo, Maria J.
Platak Jr, Michael
Allison, David B.
Parks, Christopher L.
Galler, Ricardo
Lifson, Jeffrey D.
Watkins, David I.
Wilson, Nancy A.
Plaskowski, Shari M.
Weisgrau, Kim L.
Furlott, Jessica R.
Bonaldo, Myrna C.
Santana, Marlon G. Veloso de
Rudersdorf, Richard A.
Rakasz, Eva G.
Keating, Karen D.
Chiuchiolo, Maria J.
Platak Jr, Michael
Allison, David B.
Parks, Christopher L.
Galler, Ricardo
Lifson, Jeffrey D.
Watkins, David I.
Afiliación
University of Miami. Miller School of Medicine. Department of Pathology. Miami, Florida, USA.
University of Wisconsin. Department of Medicine. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil.
University of Miami. Miller School of Medicine. Department of Pathology. Miami, Florida, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Alabama at Birmingham. Department of Biostatistics. Section on Statistical Genetics. Birmingham, Alabama, USA.
International AIDS Vaccine Initiative. AIDS Vaccine Design and Development Laboratory. Brooklyn Army Terminal. Brooklyn, New York, USA.
Leidos Biomedical Research. Inc. Frederick National Laboratory. AIDS and Cancer Virus Program. Frederick, Maryland, USA.
University of Alabama at Birmingham. Department of Biostatistics. Section on Statistical Genetics. Birmingham, Alabama, USA.
International AIDS Vaccine Initiative. AIDS Vaccine Design and Development Laboratory. Brooklyn Army Terminal. Brooklyn, New York, USA.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.
Leidos Biomedical Research. Inc. Frederick National Laboratory. AIDS and Cancer Virus Program. Frederick, Maryland, USA.
University of Miami. Miller School of Medicine. Department of Pathology. Miami, Florida, USA.
University of Wisconsin. Department of Medicine. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil.
University of Miami. Miller School of Medicine. Department of Pathology. Miami, Florida, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Wisconsin. Wisconsin National Primate Research Center. Madison, Wisconsin, USA.
University of Alabama at Birmingham. Department of Biostatistics. Section on Statistical Genetics. Birmingham, Alabama, USA.
International AIDS Vaccine Initiative. AIDS Vaccine Design and Development Laboratory. Brooklyn Army Terminal. Brooklyn, New York, USA.
Leidos Biomedical Research. Inc. Frederick National Laboratory. AIDS and Cancer Virus Program. Frederick, Maryland, USA.
University of Alabama at Birmingham. Department of Biostatistics. Section on Statistical Genetics. Birmingham, Alabama, USA.
International AIDS Vaccine Initiative. AIDS Vaccine Design and Development Laboratory. Brooklyn Army Terminal. Brooklyn, New York, USA.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.
Leidos Biomedical Research. Inc. Frederick National Laboratory. AIDS and Cancer Virus Program. Frederick, Maryland, USA.
University of Miami. Miller School of Medicine. Department of Pathology. Miami, Florida, USA.
Resumen en ingles
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.
Palabras clave en portugues
HIVPalabras clave en ingles
Human and simian immunodeficiency viruses (HIV and SIV)HIV
Vaccination regimens
T-cell responses
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