Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques

Marcio O. Lasaro, Larissa H. Haut, Xiangyang Zhou, Zhiquan Xiang, Dongming Zhou, Yan Li, Wynetta Giles-Davis, Hua Li, Jessica C. Engram, Lauren J. Dimenna, Ang Bian, Marina Sazanovich, Elizabeth M. Parzych, Raj Kurupati, Juliana C. Small, Te Lang Wu, Rachel M. Leskowitz, Nichole Klatt, Jason M. Brenchley, David A. GarberMark Lewis, Sarah J. Ratcliffe, Michael R. Betts, Guido Silvestri, Hildegund C. Ertl

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4 T cells. In addition, the two vaccinated Mamu-A01 macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalMolecular Therapy
Volume19
Issue number2
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Lasaro, M. O., Haut, L. H., Zhou, X., Xiang, Z., Zhou, D., Li, Y., Giles-Davis, W., Li, H., Engram, J. C., Dimenna, L. J., Bian, A., Sazanovich, M., Parzych, E. M., Kurupati, R., Small, J. C., Wu, T. L., Leskowitz, R. M., Klatt, N., Brenchley, J. M., ... Ertl, H. C. (2011). Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques. Molecular Therapy, 19(2), 417-426. https://doi.org/10.1038/mt.2010.238