Past exposure to adenovirus caused people to produce more T-cellsThe failure of an experimental AIDS vaccine trial two years ago may have been caused by the common cold virus.
The vaccine was intended to block the spread of HIV, which causes AIDS. But the test was canceled after volunteers who got the shots were more likely to become infected than those who got a dummy shot.
The problem, which could hamper efforts to stifle the spread of HIV in Third World countries, may have been using the common adenovirus to carry HIV material around the body to help the immune system recognize the invader. The conclusion comes from researchers reporting in Tuesday's edition of Proceedings of the National Academy of Sciences.
The test vaccine itself did not spread the illness, the team of researchers said.
However, adenovirus — which causes the common cold — is so widespread that many people have previously been exposed to it. The researchers said that prior exposure resulted in mucus membranes producing large numbers of immune cells called CD4 T-cells to fight off the adenovirus. But those are also the cells that HIV infects, providing a ready place for the AIDS virus to grow in people who had received the vaccine and were later exposed to HIV, the researchers said.
"Our research would suggest a cautious approach for the future development of adenovirus vector vaccines for use in areas of high HIV prevalence, or in individuals whose lifestyles meant that they were at higher risk of HIV infection," said Steven Patterson, lead author of the study appearing in Tuesday's edition of Proceedings of the National Academy of Sciences.
Adenovirus also used in other new vaccinesAdenovirus is also used in vaccines for tuberculosis and malaria that are under development, said Patterson, of Imperial College, London. This raises a particularly difficult problem in many areas of the world with a high rate of HIV, and high rates of TB and malaria that will be targeted by vaccines for those diseases, he said.
"If our hypothesis is correct, then the use of an adenovirus vaccine against any disease in an area of high HIV prevalence may increase the risk of HIV infection," he said.
However, Patterson noted in an e-mail, "there are scientists in the HIV vaccine field who do not believe that the adenovirus was the reason for increased number of infections in the vaccinated group."
Dr. Michael Robertson of Merck & Co., Inc., which was conducting the discontinued study, known as Step, welcomed the report as providing "additional insights.
However, "it would be premature to suggest that this provides an explanation for the Step results, and the implications for other vaccines or gene therapy are unclear," Robertson, director of Infectious Diseases/Vaccines Clinical Research at Merck, said through a spokesman.
"The unexpected findings from the Step Study have led to a major reassessment of the entire HIV vaccine field, so any advance is helpful," Robertson said.
Adenovirus is also used in some gene therapy, but Patterson said: "For most individuals undergoing gene therapy I would not expect the use of an adenovirus vector to increase their risk of HIV infection unless their lifestyle rendered them at a higher risk of HIV infection anyway."
Other viruses and bacteria are being studied for use in vaccines, as are different subtypes of adenovirus, he said.
The research was supported by the Coalition for AIDS Vaccine Discovery, the Bill and Melinda Gates Foundation, the Stephens Trust and Chelsea and Westminster Hospital, London.
The vaccine was intended to block the spread of HIV, which causes AIDS. But the test was canceled after volunteers who got the shots were more likely to become infected than those who got a dummy shot.
The problem, which could hamper efforts to stifle the spread of HIV in Third World countries, may have been using the common adenovirus to carry HIV material around the body to help the immune system recognize the invader. The conclusion comes from researchers reporting in Tuesday's edition of Proceedings of the National Academy of Sciences.
The test vaccine itself did not spread the illness, the team of researchers said.
However, adenovirus — which causes the common cold — is so widespread that many people have previously been exposed to it. The researchers said that prior exposure resulted in mucus membranes producing large numbers of immune cells called CD4 T-cells to fight off the adenovirus. But those are also the cells that HIV infects, providing a ready place for the AIDS virus to grow in people who had received the vaccine and were later exposed to HIV, the researchers said.
"Our research would suggest a cautious approach for the future development of adenovirus vector vaccines for use in areas of high HIV prevalence, or in individuals whose lifestyles meant that they were at higher risk of HIV infection," said Steven Patterson, lead author of the study appearing in Tuesday's edition of Proceedings of the National Academy of Sciences.
Adenovirus also used in other new vaccinesAdenovirus is also used in vaccines for tuberculosis and malaria that are under development, said Patterson, of Imperial College, London. This raises a particularly difficult problem in many areas of the world with a high rate of HIV, and high rates of TB and malaria that will be targeted by vaccines for those diseases, he said.
"If our hypothesis is correct, then the use of an adenovirus vaccine against any disease in an area of high HIV prevalence may increase the risk of HIV infection," he said.
However, Patterson noted in an e-mail, "there are scientists in the HIV vaccine field who do not believe that the adenovirus was the reason for increased number of infections in the vaccinated group."
Dr. Michael Robertson of Merck & Co., Inc., which was conducting the discontinued study, known as Step, welcomed the report as providing "additional insights.
However, "it would be premature to suggest that this provides an explanation for the Step results, and the implications for other vaccines or gene therapy are unclear," Robertson, director of Infectious Diseases/Vaccines Clinical Research at Merck, said through a spokesman.
"The unexpected findings from the Step Study have led to a major reassessment of the entire HIV vaccine field, so any advance is helpful," Robertson said.
Adenovirus is also used in some gene therapy, but Patterson said: "For most individuals undergoing gene therapy I would not expect the use of an adenovirus vector to increase their risk of HIV infection unless their lifestyle rendered them at a higher risk of HIV infection anyway."
Other viruses and bacteria are being studied for use in vaccines, as are different subtypes of adenovirus, he said.
The research was supported by the Coalition for AIDS Vaccine Discovery, the Bill and Melinda Gates Foundation, the Stephens Trust and Chelsea and Westminster Hospital, London.
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