A common cold virus used in an experimental HIV vaccine may have been an inappropriate vehicle for stimulating immune cells to fight HIV, a new study suggests. In 2007, researchers halted the STEP trial after it appeared that volunteers who received Merck & Co.'s vaccine candidate were more likely to later contract HIV.
The adenovirus serotype 5 (Ad5) was used as a vector to carry genetic HIV material that researchers hoped would prompt an immune response to prevent HIV's spread. Because adenovirus is a common cold virus, many people have been previously exposed to it, including some STEP trial participants.
In the new study, investigators proposed that increased HIV infection rates among Ad5-seropositive vaccine recipients "was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells." In these individuals, mucous membranes could have produced large numbers of CD4 cells, providing HIV with an abundance of the very cells the virus infects.
"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, the study's lead author.
"If our hypothesis is correct, then the use of an adenovirus vaccine against any disease in an area of high HIV prevalence may increase risk of HIV infection," Patterson said. On the other hand, "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."
"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," Dr. Michael Robertson, director of Infectious Diseases/Vaccines Clinical Research at Merck, said through a spokesperson.
The full study, "Adenovirus Vector Vaccination Induces Expansion of Memory CD4 T Cells with a Mucosal Homing Phenotype that Are Readily Susceptible to HIV-1," was published in the Proceedings of the National Academy of Sciences (2009;doi: 10.1073/pnas.0907898106).
11/16/09
UNITED STATES: Common Cold Virus May Have Foiled HIV Vaccine Test
Source: Associated Press:: Randolph E. Schmid; Courtesy of the CDC National Center for HIV, STD, and TB Prevention