View All Abstracts for Session 30
164 Prime vs. Prime-Boost Vaccinations with a Recombinant MVA Virus Expressing SHIV-89.6 env, gag, and pol Followed by Soluble gp140 Protein
P. Earl*1, L. Wyatt1, D. Montefiori2, M. Bilska2, R. Woodward3, P. Markham3, J. Malley1, T. Vogel4, T. Allen4, D. Watkins4,5, N. Miller1, and B. Moss1
1NIH, Bethesda, MD, USA; 2Duke Univ. Med. Ctr., Durham, NC, USA; 3Advanced BioSci. Labs, Inc., Kensington, MD, USA; 4Wisconsin Regional Primate Res. Ctr., Madison, USA; and 5Univ. of Wisconsin, Madison, USA
Background: Effective vaccination against HIV will likely require both humoral and cellular immunity. One potential means of achieving this is vaccination with a recombinant MVA followed by boosting with soluble envelope protein. To test this vaccination strategy in the simian-human immunodeficiency virus (SHIV) model system, we constructed a recombinant MVA expressing the env, gag, and pol genes from SHIV-89.6 (MVA/SHIV89.6).
Methods: Groups of rhesus macaques were immunized with MVA/SHIV89.6 alone or followed by boosting with soluble oligomeric 89.6 gp140. Animals were challenged with either SHIV-89.6 (Study 1) or SHIV-89.6P (Study 2). Temporal binding and neutralizing antibody titers were determined throughout the study. In a subset of animals, Mamu-*A01/CM9 tetramer binding was determined. Plasma RNA and CD4 T-cell counts were followed after challenge.
Results: Immunization with MVA/SHIV89.6 alone elicited ELISA binding antibodies in all animals and neutralizing antibodies in 5 of 15 animals. Antibody titers were enhanced in animals that received the protein boost. In addition, Mamu-A*01/CM9 tetramer binding was detected in the subset of Mamu-A*01 positive animals. In Study 1, all control and vaccinated animals except 1 became infected. However, the levels of viremia were: controls > rMVA alone > rMVA + env. Although both experimental groups had statistically significant reductions in viremia compared with the controls, the difference between the vaccine groups did not reach significance. In Study 2, the vaccinated group exhibited a 5-fold reduction in peak viremia and 10-fold reduction in the post-acute phase viremia in comparison to the controls. One year after challenge, all of the controls required euthanasia, whereas 3 of the 5 vaccinated animals remain healthy.
Conclusions: Immunization with MVA/SHIV89.6 alone or with a protein boost stimulated both arms of the immune system and resulted in significant control of viremia and delayed progression to disease after challenge with SHIV-89.6P.
Contact Author about this Abstract
