Abstract Search Browse Program and Abstracts Schedule-at-a-Glance Conference Mission & Sponsors Program Committee Contact Us


View All Abstracts for Session 30



159   Protection by SIV VLP DNA Prime/Protein Boost following Mucosal SIV Challenge Is Markedly Enhanced by IL-12/GM-CSF Coadministration  

E. O’Neill*1, I. Martinez1, Z. Israel2, F. Villinger3, M. Sidhu2, R. Stout5, D. Montefiori4, A. A. Ansari3, M. Martinez1, and E. Kraiselburd1
1Caribbean Primate Res. Ctr. and Univ. of Puerto Rico-MSC, San Juan, Puerto Rico; 2Wyeth-Lederle Vaccines, Pearl River, NY, USA; 3Emory Univ., Atlanta, GA, USA; 4Duke Univ., Durham, NC, USA; and 5Bioject Inc., Portland, OR, US

Background: Improved vaccination strategies are needed to induce protective immunity in rhesus macaques to control viral replication after a mucosal challenge with pathogenic SIVsmE660.
Methods: Groups of 5 rhesus macaques were immunized with DNA expressing SIVsmB7 VLPs (VecB7), and boosted with VLP protein (see below). DNA immunization was combined with constructs expressing rhesus IL-12 and GM-CSF. The VLP boost was coadministered with or without rhesus rIL-12, as follows:











GroupsDNA prime x3(id/im)Boost wk 39
1empty vector/IL-12/GM-CSFVLP
2empty vector/IL-12/GM-CSFVLP + rIL - 12
3VecB7VLP
4VecB7VLP + rIL - 12
5VecB7/IL-12/GM-CSFVLP
6VecB7/IL-12/GM-CSFVLP + rIL - 12
7nonenone


Results: Immunization induced both humoral and cell-mediated responses against SIV gag and env, but no neutralizing antibodies. Priming with VecB7/IL-12/GM-CSF resulted in an increase in the frequencies of animals with SIV-specific CTL. Following intrarectal challenge at week 48, viral replication was detected in all animals. Immunized monkeys showed lower levels of viral replication. After 8 months, viral loads (VL) in monkeys immunized only with VLPs were comparable to those in naïve controls. The immunized animals have remained healthy unlike control animals. Monkeys immunized with either VecB7/IL-12/GM-CSF or primed only with VecB7 and boosted with VLP/IL-12 showed a 2.5 log reduction (p < 0.03) of VL set points. Lower VL did not correlate with the presence of SIV-specific antibodies. CTL responses against SIV were observed in 4/8 Vec B7-immunized animals, which had low VL for 26 weeks.
Conclusions: Vaccination with VecB7 in combination with DNA-delivered cytokine adjuvants which favor cell-mediated responses, resulted in effective and improved control of virus replication of a highly pathogenic virus. Immune correlates of such containment of viral replication are currently under investigation.
Contact Author about this Abstract