A variety of approaches are used to evaluate the immunogenicity of a specific candidate HIV-1 vaccine, X. These approaches may or may not include testing immunogenicity of the HIV-1 vaccine itself in non-primates (e.g., rodents, rabbits, guinea pigs, etc.) or NHPs. In addition, the immunogenicity of an SIV or SHIV analogue of the HIV-1 vaccine may be tested in NHPs; this is done before NHP efficacy trials, which require challenge of NHPs with SIV or SHIV. Currently, neither immunogenicity nor challenge studies in NHPs are required preclinical assessments for candidate HIV-1 vaccines.

This strategy would be required for advancing an HIV-1 vaccine candidate to human testing.
Step 1. A NHP challenge trial to evaluate the potential efficacy of each candidate HIV-1 vaccine would be required. The NHP challenge study must include three elements: an SIV analogue of the candidate HIV-1 vaccine, an appropriate pathogenic SIV challenge isolate, and use of NHPs with diverse MHC class I haplotypes. Specific characteristics of SIV isolates that should be used in NHP challenge studies to evaluate efficacy of SIV vaccine analogues are described in the text. Pathogenic R5 SHIVs that recapitulate the key features of HIV-1 infection might be appropriate challenge viruses to estimate the ability of a neutralizing antibody-based HIV-1 vaccine candidate to prevent infection in NHPs. NHPs with diverse MHC class I haplotypes must be used to minimize selection of animals with strong natural capacity to control SIV replication even without vaccination.
Step 2. NHP immunogenicity testing of a candidate HIV-1 vaccine would only be undertaken if statistically significant protection from uncontrolled SIV replication were observed for vaccinated compared to unvaccinated NHPs in Step 1. Importantly, the immunogenicity of the HIV-1 vaccine product from a seed stock intended for clinical trials must be tested in NHPs. If strong, consistent immunogenicity of the candidate HIV-1 vaccine is observed in NHPs in Step 2, preclinical testing of toxicity and stability would proceed.
Step 3. If a candidate HIV-1 vaccine is found to be immunogenic in NHPs, nontoxic, and stable, then the vaccine product would be made using GMP procedures, vialed, and released for phase I trials in humans.