Multimodality vaccination against clade C SHIV: Partial protection against mucosal challenges with a heterologous tier 2 virus

Samir K. Lakhashe, Siddappa N. Byrareddy, Mingkui Zhou, Barbara C. Bachler, Girish Hemashettar, Shiu Lok Hu, Francois Villinger, James G. Else, Shannon Stock, Sandra J. Lee, Diego A. Vargas-Inchaustegui, Egidio Brocca Cofano, Marjorie Robert-Guroff, Welkin E. Johnson, Victoria R. Polonis, Donald N. Forthal, Erwann P. Loret, Robert A. Rasmussen, Ruth M. Ruprecht

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. This SHIV strain exhibits many properties of transmitted HIV-1, such as tier 2 phenotype (relatively difficult to neutralize), exclusive CCR5 tropism, and gradual disease progression in infected RMs. Since no human AIDS vaccine recipient is likely to encounter an HIV-1 strain that exactly matches the immunogens, we immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low-level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses.

Original languageEnglish (US)
Pages (from-to)6527-6536
Number of pages10
JournalVaccine
Volume32
Issue number48
DOIs
StatePublished - Nov 12 2014

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Keywords

  • ADCC
  • Cellular immunity
  • HIV vaccine
  • Heterologous tier 2 virus
  • Rhesus monkey
  • SHIV-C

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Lakhashe, S. K., Byrareddy, S. N., Zhou, M., Bachler, B. C., Hemashettar, G., Hu, S. L., Villinger, F., Else, J. G., Stock, S., Lee, S. J., Vargas-Inchaustegui, D. A., Cofano, E. B., Robert-Guroff, M., Johnson, W. E., Polonis, V. R., Forthal, D. N., Loret, E. P., Rasmussen, R. A., & Ruprecht, R. M. (2014). Multimodality vaccination against clade C SHIV: Partial protection against mucosal challenges with a heterologous tier 2 virus. Vaccine, 32(48), 6527-6536. https://doi.org/10.1016/j.vaccine.2014.08.065