Background:  The development of an effective AIDS vaccine remains one of the highest priorities in HIV-research. The live attenuated varicella zoster virus (VZV) Oka vaccine is known to be safe and effective for prevention of chickenpox in children and zoster in the elderly, and may have potential as a recombinant vaccine against other pathogens, including HIV. Increasing evidence suggests that an effective vaccine will require both humoral and cellular immunity, and needs rigorous in vivo testing in an animal model to satisfy those requirements, prior to use in humans. The simian model of varicella infection utilizes the highly similar counterpart virus, simian varicella virus (SVV). This study tested the hypothesis that recombinant varicella viruses expressing SIV antigens induce broad humoral and cell-mediated immune responses against SIV in the nonhuman primate.

Methods:  Recombinant simian varicella virus (rSVV) expressing the SIVenv (gp130) and SIVgag antigens were constructed. A cosmid-based SVV genetic recombination system was used to insert SIVenv and SIVgag genes within the nonessential SVV glycoprotein C gene. Preclinical testing of the recombinant virus vaccines was conducted in the African green monkey, a species highly susceptible to infection with SVV. Animals (n = 9), were divided into 4 groups and given subcutaneous and intratracheal inoculations with:  rSVV-SIVgag, rSVV-SIVenv,  both gag and env recombinants, and wild type SVV as control.

Results:  In cell culture, rSVV-SIVenv and rSVV-SIVgag replicated as efficiently as wild type SVV. Expression of SIV transcripts in infected Vero cells was confirmed by real time polymerase chain reaction (RT-PCR), while antigens were confirmed by immunofluorescence and immunoblot. In vivo, and within 2 weeks of immunization, all animals showed signs of acute varicella infection, with viremia, fever, and rash, and then completely resolved. The booster immunization at 6 weeks was well tolerated and without recurrent clinical signs. Humoral immune responses to SIVenv and SIVgag were demonstrated with increased titers following the boost. Cellular immune responses against SIVenv were detected by interferon-gamma (IFN-γ) ELISpot assay.

Conclusions:  Results demonstrate that rSVV-SIV vaccines stimulate humoral and cellular immune responses against SIV antigens. Further studies are necessary to evaluate their ability to protect against simian acquired immunodeficiency syndrome following SIV challenge.