An attenuated vaccine for AIDS?

Abstract

One of the few bright prospects in AIDS research is the findings from a study of an attenuated SIV vaccine in monkeys. The vaccine consists of SIV with the nef region deleted (SIVmac239). All 6 monkeys vaccinated with the nef-deleted virus were still healthy and alive 5 years after vaccination, while 11 of the 12 rhesus monkeys administered the virulent SIVmac died. The case monkeys were challenged with virulent SIV at 2.25 years and were completely protected. Other researchers used an attenuated SIV C3 as the live vaccine and a virulent virus J5 as the challenge. Both these viruses have identical sequences, except for 7 nucleotide differences in the nef gene or 3' long terminal repeat [LTR]). The researchers steadily infected the vaccinated animals with C8. They challenged the animals with cell-free J5 or cell-associated J82. They could not recover any challenge virus from the animals and could not detect J5 or J82 by polymerase chain reaction. The researchers believe that the stimulation of a cytotoxic T-cell response may explain the immune mechanism for the protective effect of these living attenuated vaccines. Mimicking this response with a non-living vaccine would greatly increase the likelihood of an AIDS vaccine. A very real fear is reversion to virulence of a dormant-attenuated HIV. The high rate of replication of HIV, the established detection of antigenic and drug-resistant mutants, and possible infection of other target cells (e.g., in the central nervous system) reinforce fears of an attenuated HIV vaccine. Nevertheless, the promise of the attenuated vaccine for an approach to AIDS control and the lack of progress of other methods behooves researchers to investigate the safety of a living vaccine in macaques. Eventually, it may be possible to reinfect animals already infected with a virulent virus and see whether this can stop progression of the disease.