Vaccination against heterologous R5 clade C SHIV

Prevention of infection and correlates of protection

Samir K. Lakhashe, Wendy Wang, Siddappa Nagadenahalli Byrareddy, Girish Hemashettar, Patricia Polacino, Shiu Lok Hu, François Villinger, James G. Else, Francis J. Novembre, John K. Yoon, Sandra J. Lee, David C. Montefiori, Ruth M. Ruprecht, Robert A. Rasmussen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.

Original languageEnglish (US)
Article numbere22010
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - Jul 26 2011

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Simian Immunodeficiency Virus
Human immunodeficiency virus
Virus Diseases
Human immunodeficiency virus 1
Viruses
Cellular Immunity
cell-mediated immunity
Vaccination
vaccination
HIV
Simian immunodeficiency virus
HIV-1
HIV Envelope Protein gp160
viremia
pandemic
dosage
Macaca mulatta
neutralizing antibodies
humoral immunity
infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lakhashe, S. K., Wang, W., Byrareddy, S. N., Hemashettar, G., Polacino, P., Hu, S. L., ... Rasmussen, R. A. (2011). Vaccination against heterologous R5 clade C SHIV: Prevention of infection and correlates of protection. PloS one, 6(7), [e22010]. https://doi.org/10.1371/journal.pone.0022010

Vaccination against heterologous R5 clade C SHIV : Prevention of infection and correlates of protection. / Lakhashe, Samir K.; Wang, Wendy; Byrareddy, Siddappa Nagadenahalli; Hemashettar, Girish; Polacino, Patricia; Hu, Shiu Lok; Villinger, François; Else, James G.; Novembre, Francis J.; Yoon, John K.; Lee, Sandra J.; Montefiori, David C.; Ruprecht, Ruth M.; Rasmussen, Robert A.

In: PloS one, Vol. 6, No. 7, e22010, 26.07.2011.

Research output: Contribution to journalArticle

Lakhashe, SK, Wang, W, Byrareddy, SN, Hemashettar, G, Polacino, P, Hu, SL, Villinger, F, Else, JG, Novembre, FJ, Yoon, JK, Lee, SJ, Montefiori, DC, Ruprecht, RM & Rasmussen, RA 2011, 'Vaccination against heterologous R5 clade C SHIV: Prevention of infection and correlates of protection', PloS one, vol. 6, no. 7, e22010. https://doi.org/10.1371/journal.pone.0022010
Lakhashe, Samir K. ; Wang, Wendy ; Byrareddy, Siddappa Nagadenahalli ; Hemashettar, Girish ; Polacino, Patricia ; Hu, Shiu Lok ; Villinger, François ; Else, James G. ; Novembre, Francis J. ; Yoon, John K. ; Lee, Sandra J. ; Montefiori, David C. ; Ruprecht, Ruth M. ; Rasmussen, Robert A. / Vaccination against heterologous R5 clade C SHIV : Prevention of infection and correlates of protection. In: PloS one. 2011 ; Vol. 6, No. 7.
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