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11 Immunization of Baboons (Papio cynocephalus hamadryas) Using a DNA Vaccine Formulated with Cationic Liposomes and Genetic Adjuvants
C. P. Locher*1, S. A. Witt1, B. M. Ashlock1, G. L. Kropp1, R. M. Grant1, A. M. Schmidt2, M. Agy2, D. M. Anderson2, C. J. Wheeler3, and J. A. Levy1
1Univ. of California, San Francisco, USA; 2Univ. of Washington, Seattle, USA; and 3Vical Corp., San Diego, CA, USA
Background: Since genetic adjuvants improve immune responses to DNA vaccines in rodents, we sought to determine if granulocyte-macrophage colony stimulating factor (GM-CSF) and B7-2 could improve immune responses and protection against HIV-2 infection in baboons.
Methods: In the first group, 4 baboons were immunized 4 times using codon-optimized HIV-2 gp140 env, p55 gag, nef, and tat DNA constructs formulated with cationic liposomes. In the second group, 4 baboons were immunized with the same DNA vaccine formulation containing 1 mg each of baboon GM-CSF and B7-2. In the control groups, 2 baboons were immunized with a plasmid DNA vaccine formulation only and 2 other baboons were immunized with a plasmid DNA formulation combined with GM-CSF and B7-2. Cytotoxic T-lymphocyte activity, CD8+ cell-mediated suppression, and antibody responses were measured. The two-tailed Mann Whitney U test was used to evaluate statistical significance between the groups of baboons.
Results: We found that the CTL activity was significantly enhanced in the group of baboons that received the genetic adjuvants compared with the groups that received the HIV-2 DNA vaccine alone. The CTL activity in the genetic adjuvant group was also present in the CD4+ cell population. After infection with HIV-2, CD4+ T cells from the genetic adjuvant group were resistant to HIV-2 replication in vitro. In contrast to the vigorous cellular immune responses induced by this vaccine formulation, antibodies to HIV-2 remained at low levels.
Conclusions: GM-CSF and B7-2 enhance the production of antigen-specific CTL (p = 0.020), which is also present in the CD4+ cell population (p = 0.013). Moreover, these genetic adjuvants can induce resistance of CD4+ cells to HIV-2 infection in vitro (p = 0.049).
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