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44 Working toward an AIDS Vaccine
H. L. Robinson
Emory Vaccine Ctr. and Yerkes Primate Res. Ctr., Atlanta, GA, USA
Background: In 1997(1999 we showed that DNA priming plus recombinant poxvirus boosters were more effective than DNA alone or DNA plus protein boosters in raising protective immunity against SHIV challenges. To further define parameters for a DNA/poxvirus vaccine, a multi-group preclinical trial was undertaken as a collaborative effort between the Emory Vaccine Ctr., Bernard Moss’s laboratory of the NIAID, and Janet McNicholl’s laboratory at the CDC.
Methods: Rhesus macaques were immunized with high (2.5 mg) or low (0.25 mg) doses of a SHIV-89.6 Gag-Pol-Env or Gag-Pol expressing DNA at 0 and 8 weeks and boosted with a Gag-Pol-Env or Gag-Pol SHIV-89.6 recombinant MVA (rMVA) at 24 weeks. One Gag-Pol-Env group received recombinant 89.6 gp120 protein in alum at the second DNA immunization and at the rMVA booster. One Gag-Pol-Env group received GM-CSF DNA at both DNA administrations. Seven months following the third immunization when vaccine-raised responses were in memory, the macaques were administered an intrarectal SHIV-89.6P challenge. The trials were monitored for cellular and humoral responses to the vaccine and the challenge infection, and for levels of post-challenge viral RNA.
Results: The 89.6P challenge infected all of the vaccinated as well as the control animals. The best control of the challenge was achieved in groups receiving the Gag-Pol-Env DNA/MVA vaccine. Nineteen out of 20 animals receiving a high dose DNA prime have controlled the challenge at or below the level of detection of viral RNA for more than 8 months. Twelve out of 12 animals receiving the low dose i.d. DNA prime with or without GM-CSF DNA also have controlled the challenge to levels at, or below, the background for detection. The GM-CSF DNA did not make a difference in protection. The Gag-Pol immunogens were not as effective as the Gag-Pol-Env immunogens with some Gag-Pol animals succumbing to AIDS within 10 months of challenge. The added gp120 protein also did not provide better control of the challenge infection; in this group 3 out of 8 animals have a persistent high viremia.
Conclusions: We plan to go forward with a Gag-Pol-Env DNA/MVA vaccine.
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