SIV nucleocapsid mutant DNA vaccine: immunization and challenge

We have found that cells transfected with nucleocapsid mutant proviral DNA results in expression of non-infectious virus particles, containing the full complement of viral proteins, deficient in genomic RNA which can bind to and enter susceptible cells. Duplication of this in vivo should expose the immune system to all steps in virus replication and could mimic infection with attenuated virus and may offer a viable vaccine strategy for control of HIV infection. To test this strategy in vivo, five macaques were inoculated intramuscularly with a nucleocapsid mutant (delta2ZF) SIV DNA. Anti-SIV antibodies was detected in two of the animals after DNA inoculations showing that the proviral DNA had been expressed. Four control animals received vector plasmid DNA lacking the SIV construct. When the animals were challenged with infectious SIVmne, all four control animals became persistently infected, with high plasma viral levels (10(5)-10(6) RNA genome equivalents/ml). Virus was readily isolated from PBMCs and three of the four control animals show markedly declining CD4 cells. Only one animal in the DNA-vaccinated group showed virus levels comparable to the controls. Plasma virus levels were either undetectable or 2 to 3 logs less than control animals. All DNA-vaccinated animals, except one, continue to show normal CD4 cell counts. To enhance expression levels, CMV have been used to replace the viral LTRs and initial transfections have shown significantly higher levels of viral particle expression. Current status of the vaccine results will be presented.

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