• Vaccine Name: Gag-VRPs
• Target Pathogen: Human Immunodeficiency Virus
• Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
• Vaccine Ontology ID: VO_0000822
• Antigen: HIV matrix-capsid portion of Gag, envelope gp160, secreted gp140, cloned SIVsm H-4i, SIVsm E660 (Davis et al., 2002)
• Preparation: Gag-VRPs is a cocktail vaccine of V3014-packaged VRPs expressing the SIVsm H-4i nonmyristylated matrix-capsid region, full-length gp160, and a secreted form of gp160 (gp140). Structural proteins for packaging of replicon RNA into VRPs are expressed from separate helper RNAs. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIVsm H-4i were mixed in a cocktail and used to immunize macaques (Davis et al., 2002).

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: VRPs with wild-type glycoprotein spikes were inoculated into the footpads of mice (Davis et al., 2002).
• Persistence: At 11 months post-boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins (Caley et al., 1999).
• Immune Response: In BALB/c mice, the two vectors elicited cellular immune responses to MA/CA as determined by bulk CTL assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins (Caley et al., 1999).

Monkey Response

• Host Strain: rhesus monkey (Macaca mulatta)
• Vaccination Protocol: A cocktail vaccine of V3014-packaged VRPs expressing the SIVsm H-4i nonmyristylated matrix-capsid region, full-length gp160, and a secreted form of gp160 (gp140) was used to immunize rhesus macaques. Animals were given each VRP subcutaneously in the arm and later were challenged by the intrarectal (IR) route. Control animals received an equivalent dose of HA-VRPs (Davis et al., 2002).
• Immune Response: Both humoral and cellular immune responses were induced. On the day of challenge, all vaccinated animals had neutralizing antibody to the homologous SIVsm H-4, most had CTL specific for Gag, Env, or both. The animals were followed for a period of 40 weeks postchallenge, and although vaccination did not prevent infection by the high dose IR challenge, several protective effects of vaccination were seen. Peak virus titers in plasma were reduced, and the range of peak titers was much smaller for the controls, suggesting that a clear protective effect against the acute phase of infection was induced in some of the vaccinated animals (Davis et al., 2002).
• Side Effects: No side effects were encountered (Davis et al., 2002).
• Challenge Protocol: Animals were given a dose of VRP subcutaneously in the arm and 1 month later were challenged by the intrarectal (IR) route. Control animals received an equivalent dose of HA-VRPs. The challenge virus was the highly virulent swarm SIVsm E660 (Davis et al., 2002).
• Efficacy: Animals were followed for a period of 40 weeks postchallenge, and although vaccination did not prevent infection by the high dose IR challenge, several protective effects of vaccination were seen. Four of six vaccinated animals, as compared to one of six controls, showed virus loads below 1,700 copies per ml at the “set point” (23 weeks postchallenge). By 41 weeks postchallenge, when the experiment was terminated, there was a significant decrease in the mean plasma virus load in the vaccinated animals compared to that in the controls. Most vaccinated animals showed virus loads below the “set point” (23 weeks postchallenge). By 41 weeks postchallenge, when the experiment was terminated, there was a significant decrease in the mean plasma virus load in the vaccinated animals compared to that in the controls. Finally, the CD4C cells of the vaccinated animals were preserved and even increased postchallenge compared to those of the controls. In fact, in the vaccinated animals, there is a clear correlation between increased CD4C cells and lowered viral load (Davis et al., 2002).