Scientific and policy challenges to development of an AIDS vaccine

Vector-based candidate vaccines suppressed viral load and, in some cases, slowed disease progression in the macaque SIV and SIV-HIV chimera (SHIV) challenge models.11 Immunisation with a live attenuated SIV vaccine robustly protected macaques against subsequent challenge by mucosal or intravenous routes.12,13 Passive administration of broadly neutralising human HIV-antibodies protected monkeys against vaginal challenge with pathogenic SHIV.14,15 Taken together, these findings suggest that delivery of the correct combination of antigens in an effective formulation should enable induction of immunological protection in humans. A live SIV vaccine, attenuated by deletion of the nef gene SIVAne/, protected monkeys challenged with homologous pathogenic SIV more than 2 years after immunisation,12,13 and a retrospective analysis showed that live attenuated SIV was more protective than other vaccine types.16 However, SIVΔnef establishes a persistent state in the vaccinated host, can revert to virulence in some animals,17 and was pathogenic to neonatal macaques when given at high doses.18,19 An Australian cohort of patients who were naturally infected with nef-deleted HIV eventually had diminished CD4+ T cells and a slow progression towards AIDS.20 A live attenuated AIDS vaccine would also probably face regulatory controls because of concerns about the theoretical potential for insertional oncogenesis due to chromosomal integration of the HIV provirus.\n This will raise tough issues for regulatory agencies that will have to develop specific guidelines for testing of such vectors and reassess their risks and benefits.