Important note: Information in this article was accurate in March 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, March 1, 1999
Daniel J. DeNoon, Senior Editor
It seems doubtful, however, whether live virus with attenuated replicative capacity can ever be considered safe.
F. Titti and colleagues at Italy's NIH Laboratory of Virology vaccinated cynomolgus monkeys with the C8 variant of SIVmac251/32H, which has a 12-bp deletion in its nef gene. The animals first resisted challenge at 40 weeks with SIVmac251/BK28; 103 weeks later they resisted challenge with SIVmac251/32H/63M. Four years after infection with the vaccine strain they were challenged with SHIV89.6P, a highly pathogenic hybrid virus made up of the HIV envelope and the SIV core. Again, all animals were protected. None appeared to be infected with anything but the original vaccine strain.
"These results provide evidence that a live attenuated SIV vaccine could provide effective long term protection even against a heterologous challenge with highly divergent envelope sequences," Titti and colleagues concluded.
Titti reported the study findings in a poster discussion session of the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
These impressive findings are far less sensational than they would have been before Harvard's Ruth Ruprecht reported at the 1998 World AIDS Conference that many monkeys given similar vaccines have developed AIDS or symptoms of SIV disease.
Timothy W. Baba, Ruprecht, and colleagues recently published their studies in the journal Nature Medicine ("Live Attenuated, Multiply Deleted Simian Immunodeficiency Virus Causes AIDS in Infant and Adult Macaques," Nat Med 1999 Feb;5(2):194-203.
"We conclude that a live attenuated virus vaccine based on attenuation of replicative capacity rather than attenuation of virulence may cause AIDS and should not be considered as a candidate for a human AIDS vaccine," Baba et al. wrote.
And attenuation of virulence would be a clever trick: to date, no special virulence factor has been found for HIV, as it was for the live attenuated Sabin poliovirus vaccine.
Still, many are unwilling to abandon hope that the most effective AIDS vaccine described to date must be relegated to the realm of experimental studies rather than practical medicine.
"What is needed now is to focus attention on the safety and efficacy of the next generation of even more heavily attenuated AIDS vaccines," wrote R. Paul Johnson of the New England Primate Center and Harvard Medical School in a commentary on the Baba et al. studies ("Live Attenuated AIDS Vaccines: Hazards and Hopes," Nat Med 1999 Feb;5(2):154-5.
Johnson is a member of the Ronald Desrosiers team that first created and tested multiply deleted, live attenuated SIV vaccines.
"The findings of Baba and co-workers clearly raise substantial concerns about the safety of a live attenuated HIV vaccine," he concluded. "But given the magnitude of the epidemic we face and the limited tools available to stem the exponentially rising tide of HIV infection, it is premature to abandon one of our most effective AIDS vaccine approaches so far."
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