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228 Inclusion of a Protein Booster in a DNA Priming and MVA Boosting Protocol for an AIDS Vaccine
S. L. Buge*1, M. Ma1, R. Amara2, L. Wyatt3, P. Earl3, B. Grimm4, F. Villinger4, J. Altman2, B. Moss3, S. I. Strapans2, N. L. Kozyr2, D. C. Montefiori5, Y. Xu2, S. O’Neil2, J. G. Herndon2, H. M. McClure2, H. Robinson2, and J. McNicholl1
1CDC, Atlanta, GA, USA; 2Regional Primate Ctr., Atlanta, GA, USA; 3NIH, Bethesda, MD, USA; 4Emory Univ. Sch. of Med., Atlanta, GA, USA; and 5Duke Univ. Med. Ctr., Durham, NC, USA
Background: It has been suggested that adding gp 120 protein to DNA or live vector vaccines might enhance protection.
Methods: To test this we immunized 16 rhesus macaques by I.D. Bioject injection at weeks 0 and 8 with 2.5 mg of a DNA vaccine expressing SIV Gag, Pol, Vif, Vpr, and Vpx and HIV Env, Tat, and Rev. Animals were boosted at week 24 with 1 ( 108 pfu of recombinant MVA (rMVA) expressing SIV Gag-Pol and HIV Env. At weeks 8 and 24, half of the animals also received I.M. inoculations of 300 mug of 89.6 gp 120 in alum. Two control animals received empty DNA vector and wild-type MVA boosting. Animals were challenged intrarectally with SHIV 89.6P at 7 months after the MVA booster. T-cell responses were measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICC), and proliferative assays.
Results: ELISPOT assays with peptide pools demonstrated broad T-cell responses against Gag and Env. Animals receiving gp120 protein boosters had a higher incidence of ELISPOTS recognizing N-terminal env epitopes compared with non-gp 120-boosted animals. Following the 8-week immunizations and also post challenge, gp 120-boosted animals had enhanced proliferative responses compared with the group not receiving protein. The DNA/MVA vaccine controlled the infection, rapidly reducing viral loads to near or below 1,000 copies of viral RNA/ml of blood, and was associated with a burst of antiviral T cells in both groups. However, the gp 120-immunized animals showed lower T-cell responses at the DNA/MVA memory phase and at the challenge peak and had higher levels of plasma viral RNA at all sampled points. The gp 120-immunized animals also showed enhanced ELISA but not neutralizing Ab.
Conclusions: Inclusion of alum-adjuvanted gp120 in a multiprotein DNA/MVA vaccine enhanced ELISA but not neutralizing Ab and was associated with less effective viral control, although CD4 cells were maintained.
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