Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: Efficacy against repeated mucosal R5 clade C SHIV challenges

Samir K. Lakhashe, Vijayakumar Velu, Gaia Sciaranghella, Nagadenahalli B. Siddappa, Janet M. DiPasquale, Girish Hemashettar, John K. Yoon, Robert A. Rasmussen, Feng Yang, Sandra J. Lee, David C. Montefiori, Francis J. Novembre, François Villinger, Rama Rao Amara, Maria Kahn, Shiu Lok Hu, Sufen Li, Zhongxia Li, Fred R. Frankel, Marjorie Robert-GuroffWelkin E. Johnson, Judy Lieberman, Ruth M. Ruprecht

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus >90%; these RM also had strong SIV Gag-specific proliferation of CD8 + T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4 + T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection.

Original languageEnglish (US)
Pages (from-to)5611-5622
Number of pages12
JournalVaccine
Volume29
Issue number34
DOIs
StatePublished - Aug 5 2011

Fingerprint

Human immunodeficiency virus 1
Macaca mulatta
HIV-1
Vaccination
vaccination
Proteins
proteins
Viremia
viremia
Neutralizing Antibodies
neutralizing antibodies
viruses
HIV Envelope Protein gp160
Vaccines
Primate Lentiviruses
T-lymphocytes
HIV
vaccines
Viruses
T-Lymphocytes

Keywords

  • HIV/AIDS vaccine
  • Live attenuated Listeria monocytogenes
  • Live oral vaccine
  • Multimeric HIV clade C gp160
  • Prime-boost vaccination
  • Replication-competent adenovirus
  • α4β7 integrin

ASJC Scopus subject areas

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

Cite this

Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein : Efficacy against repeated mucosal R5 clade C SHIV challenges. / Lakhashe, Samir K.; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B.; DiPasquale, Janet M.; Hemashettar, Girish; Yoon, John K.; Rasmussen, Robert A.; Yang, Feng; Lee, Sandra J.; Montefiori, David C.; Novembre, Francis J.; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R.; Robert-Guroff, Marjorie; Johnson, Welkin E.; Lieberman, Judy; Ruprecht, Ruth M.

In: Vaccine, Vol. 29, No. 34, 05.08.2011, p. 5611-5622.

Research output: Contribution to journalArticle

Lakhashe, SK, Velu, V, Sciaranghella, G, Siddappa, NB, DiPasquale, JM, Hemashettar, G, Yoon, JK, Rasmussen, RA, Yang, F, Lee, SJ, Montefiori, DC, Novembre, FJ, Villinger, F, Amara, RR, Kahn, M, Hu, SL, Li, S, Li, Z, Frankel, FR, Robert-Guroff, M, Johnson, WE, Lieberman, J & Ruprecht, RM 2011, 'Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: Efficacy against repeated mucosal R5 clade C SHIV challenges', Vaccine, vol. 29, no. 34, pp. 5611-5622. https://doi.org/10.1016/j.vaccine.2011.06.017
Lakhashe, Samir K. ; Velu, Vijayakumar ; Sciaranghella, Gaia ; Siddappa, Nagadenahalli B. ; DiPasquale, Janet M. ; Hemashettar, Girish ; Yoon, John K. ; Rasmussen, Robert A. ; Yang, Feng ; Lee, Sandra J. ; Montefiori, David C. ; Novembre, Francis J. ; Villinger, François ; Amara, Rama Rao ; Kahn, Maria ; Hu, Shiu Lok ; Li, Sufen ; Li, Zhongxia ; Frankel, Fred R. ; Robert-Guroff, Marjorie ; Johnson, Welkin E. ; Lieberman, Judy ; Ruprecht, Ruth M. / Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein : Efficacy against repeated mucosal R5 clade C SHIV challenges. In: Vaccine. 2011 ; Vol. 29, No. 34. pp. 5611-5622.
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AU - Sciaranghella, Gaia

AU - Siddappa, Nagadenahalli B.

AU - DiPasquale, Janet M.

AU - Hemashettar, Girish

AU - Yoon, John K.

AU - Rasmussen, Robert A.

AU - Yang, Feng

AU - Lee, Sandra J.

AU - Montefiori, David C.

AU - Novembre, Francis J.

AU - Villinger, François

AU - Amara, Rama Rao

AU - Kahn, Maria

AU - Hu, Shiu Lok

AU - Li, Sufen

AU - Li, Zhongxia

AU - Frankel, Fred R.

AU - Robert-Guroff, Marjorie

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KW - Replication-competent adenovirus

KW - α4β7 integrin

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