AEGiS-15IAC: Novel forms of DNA vaccines decrease viremia in juvenile and neonatal macaques upon SIVmac251 challenge.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Novel forms of DNA vaccines decrease viremia in juvenile and neonatal macaques upon SIVmac251 challenge.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1344)

Felber BK, Rosati M, Roth P, von Gegerfelt A, Alicea C, Valentin A, Franchini G, Markham P, Venzon D, Van Rompay K, Marthas ML, Pavlakis GN
National Cancer Institute at Frederick, Frederick, United States

BACKGROUND: We explored further optimization of antigen presentation by DNA vaccination by testing a new generation of vaccine vectors, which produce either secreted or intracellularly degraded antigens.

METHODS: Viral protein genes were fused either to the secreted chemokine MCP-3 (targeting the viral proteins to the secretory pathway); or to a beta-catenin peptide (targeting the viral proteins to the proteasomal degradation pathway). Two different studies, one in juvenile and one in neonatal macaques were performed.

RESULTS: Juvenile macaques vaccinated with MCP-gag and env fusions developed improved and more uniform humoral responses. Macaques immunized with a combination of three forms of antigens showed the broadest immune responses (T-helper, CTL responses, antibody levels) and showed statistically significant lower virus loads compared to naïve animals [p=0.013 Repeated measures (ANOVA)] upon mucosal pathogenic challenge. These animals continued to show reduced virus load for more than 30 weeks post challenge. Interestingly, we found correlation with CTL responses to env in those animals controlling viremia after challenge. In a second study, 8 neonatal macaques were vaccinated with a combination of the further optimized DNA vaccine vectors and were challenged by multiple low doses of a pathogenic SIV. Six of 8 animals were infected, compared to 7 of 8 non-vaccinated controls. The virus loads in vaccinated animals were significantly lower compared to controls (p=0.029) for the 12 weeks following challenge.

CONCLUSIONS: These data show that the combination of novel forms of DNA vaccines induced an immune response able to reduce viremia by the pathogenic SIV challenge. This was observed in two different trials using juvenile and neonatal macaques, respectively. Therefore, vectors expressing such modified antigens may improve vaccination results either alone or in combination with other vaccine modalities.

Keywords: AEGIS, Vaccines, DNA, Macaca, SIV, Viremia, Vaccination, Genes, env, Infant, Newborn, Adolescent, Animal, Humans, immunology, genetics

040711
ThOrA1344