Vaccination with gag, vif, and nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239

Mauricio Martins, Nancy A. Wilson, Shari M. Piaskowski, Kim L. Weisgrau, Jessica R. Furlott, Myrna C. Bonaldo, Marlon G. Veloso de Santana, Richard A. Rudersdorf, Eva G. Rakasz, Karen D. Keating, Maria J. Chiuchiolo, Michael Piatak Jr. M., David B. Allison, Christopher L. Parks, Ricardo Galler, Jeffrey D. Lifson, David Watkins

Research output: Contribution to journalArticle

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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

Original languageEnglish
Pages (from-to)7493-7516
Number of pages24
JournalJournal of Virology
Volume88
Issue number13
DOIs
StatePublished - Jan 1 2014

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nef Genes
vif Genes
gag Genes
Recombinant DNA
virus replication
recombinant DNA
Epitopes
Vaccination
Vaccines
vaccination
Mycobacterium bovis
vaccines
epitopes
T-Lymphocytes
T-lymphocytes
Yellow Fever Vaccine
Yellow fever virus
HIV
Antigens
Simian Immunodeficiency Virus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Vaccination with gag, vif, and nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239. / Martins, Mauricio; Wilson, Nancy A.; Piaskowski, Shari M.; Weisgrau, Kim L.; Furlott, Jessica R.; Bonaldo, Myrna C.; Veloso de Santana, Marlon G.; Rudersdorf, Richard A.; Rakasz, Eva G.; Keating, Karen D.; Chiuchiolo, Maria J.; Piatak Jr. M., Michael; Allison, David B.; Parks, Christopher L.; Galler, Ricardo; Lifson, Jeffrey D.; Watkins, David.

In: Journal of Virology, Vol. 88, No. 13, 01.01.2014, p. 7493-7516.

Research output: Contribution to journalArticle

Martins, M, Wilson, NA, Piaskowski, SM, Weisgrau, KL, Furlott, JR, Bonaldo, MC, Veloso de Santana, MG, Rudersdorf, RA, Rakasz, EG, Keating, KD, Chiuchiolo, MJ, Piatak Jr. M., M, Allison, DB, Parks, CL, Galler, R, Lifson, JD & Watkins, D 2014, 'Vaccination with gag, vif, and nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239', Journal of Virology, vol. 88, no. 13, pp. 7493-7516. https://doi.org/10.1128/JVI.00601-14
Martins, Mauricio ; Wilson, Nancy A. ; Piaskowski, Shari M. ; Weisgrau, Kim L. ; Furlott, Jessica R. ; Bonaldo, Myrna C. ; Veloso de Santana, Marlon G. ; Rudersdorf, Richard A. ; Rakasz, Eva G. ; Keating, Karen D. ; Chiuchiolo, Maria J. ; Piatak Jr. M., Michael ; Allison, David B. ; Parks, Christopher L. ; Galler, Ricardo ; Lifson, Jeffrey D. ; Watkins, David. / Vaccination with gag, vif, and nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239. In: Journal of Virology. 2014 ; Vol. 88, No. 13. pp. 7493-7516.
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AU - Bonaldo, Myrna C.

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AU - Rudersdorf, Richard A.

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AU - Keating, Karen D.

AU - Chiuchiolo, Maria J.

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