The final nail is in the coffin for the now largely refuted theory that the human immunodeficiency virus type 1 (HIV-1) crossed into humans as a result of contamination of oral polio vaccine (OPV), according to a new study. In the April 22 Nature, Michael Worobey and colleagues report that the chimpanzees claimed to be the source of simian immunodeficiency virus (SIVcpz) that crossed over actually contain a SIVcpz unrelated to HIV-1.

“Scientifically, this paper spells the end of the OPV theory,” said Edward Holmes, from the University of Oxford, who was not involved in the study.

The OPV/AIDS theory holds that chimpanzees from the Kisangani (previously Stanleyville) area in the Democratic Republic of Congo that were purportedly used in the preparation of OPV transmitted a SIVcpz to humans. Evidence against this has been piling up, first with the absence of SIVcpz or chimpanzee DNA in old OPV stocks and then with data suggesting HIV originated 30 years before the OPV trails.

“Although there is an abundance of evidence against the OPV theory, the one thing missing [until this paper] was an analysis of the SIV strains in the chimpanzee populations claimed to be the origin of HIV-1 under the OPV theory,” said Holmes.

“I first traveled to the Congo in 2000, along with W.D. Hamilton and Jeff Joy,” said Michael Worobey, assistant professor at the University of Arizona and lead author of the study. The samples obtained from this trip were suggestive, so alone, Worobey returned to the Congo in 2003. “This time we hit pay dirt, with one of the fecal samples being positive for SIV viral genetic material,” Worobey told The Scientist.

This sample turned out to be positive for gag and gp41/nef viral sequences, confirming the natural infection of Kisangani chimpanzees with SIVcpz. Analysis of these sequences revealed that this SIVcpz virus was highly divergent from HIV-1, revealing that Kisangani chimpanzees were not the source SIVcpz that crossed over to humans.

“This final proof was necessary because previous evidence against the theory, though damning, was somewhat indirect. This is as direct as you could hope for,” Worobey told The Scientist.

“Lack of chimpanzee DNA in archival stocks of OPV, together with origin of HIV dating at least 30 years prior to OPV trials in central Africa and now providing evidence that Kisangani apes contain a SIVcpz lineage not related to HIV-1, provide convincing evidence that OPV trials did not result in the HIV infection,” said Renu Lal, from the US Centers for Disease Control and Prevention, who was not involved in the study.

Bette Korber, staff scientist at Los Alamos National Laboratory, agreed, stating the report shows the exact opposite of what the OPV/AIDS theory would predict. “[Worobey and colleagues] completed the circle, and all tests that could be done with current methods have been completed. Nothing supports the OPV hypothesis,” Korber told The Scientist.

Korber, who was not involved in the study, said she hopes that this additional work will help in the drive to eradicate polio globally, stressing that the now refuted speculation on the OPV/AIDS theory never suggested that modern OPV vaccines were contaminated.

“We are very close to eradicating polio globally, a sweet triumph for humanity if we can accomplish it. Hopefully the article will help resolve the confusion that surrounds this last push in this great undertaking,” Korber told The Scientist.

“It would be nice if these findings could eliminate some of the fears and suspicions that hang over polio vaccines currently in countries like Nigeria. Polio vaccines weren't infected with AIDS viruses in the 1950s, and they're not now either, and driving that message home can only be a good thing,” said Worobey.