From The Scientist by Jet Akst.
New findings have disproved a leading explanation for why an experimental HIV vaccine made subjects more susceptible to the virus, reopening the door for further HIV vaccine efforts based on similar principles.
The Merck-funded STEP study, which used an adenoviral vector to deliver an HIV vaccine candidate, was halted in 2007 after the data suggested the vaccine increased the risk of HIV infection. Researchers thought the effect might be due to an immune reaction to the viral vector, but two studies published online in Nature Medicine today show this is not the case.
"Both of these papers show that's not a possible explanation," said molecular immunologist David Weiner of the University of Pennsylvania, who was not involved in the research.
"Overall this is a positive and optimistic message for the field," said immunologist Dan Barouch, chief of Harvard University's Division of Vaccine Research and the lead author of one of the studies. "Other vaccine vectors can and should be further pursued in clinical trials."
Individuals who have previously been exposed to adenovirus serotype 5 (Ad5) -- a common cold virus -- have more Ad5-specific antibodies in their blood; that is, they are Ad5 seropositive. Analysis of the trial suggested that Ad5-seropositive subjects contracted HIV at a higher rate when they received the vaccine as opposed to the placebo. Researchers hypothesized that Ad5-seropositive individuals might be more sensitive to the Ad5 vector, and consequently, could "mount a more rapid, larger immune response," explained molecular biologist Alan Bernstein, executive director of Global HIV Vaccine Enterprise, who was not involved in the research. Because HIV attacks activated T cells, increased T-cell counts would provide more plentiful targets for HIV infection, and could thereby explain the boost in susceptibility.
The current studies analyzed frozen blood samples from two different precursor trials to the STEP study, and in both cases, the research teams disproved the idea that prior exposure to the Ad5 vector equated to higher T-cell counts. In the study led by Barouch, approximately 90% of subjects had Ad5-specific T cells prior to vaccination, but very few had Ad5-specific antibodies. This demonstrated that the two measures of immunity -- Ad5-specific antibodies and Ad5-specific T cells -- are not correlated, meaning that that Ad5 seropositivity cannot be used to predict levels of Ad5-specific T cells prior to vaccination.
(For the full story please visit www.The-Scientist.com)
New findings have disproved a leading explanation for why an experimental HIV vaccine made subjects more susceptible to the virus, reopening the door for further HIV vaccine efforts based on similar principles.
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FHuman Immunodeficiency Virus Image: NIAID |
"Both of these papers show that's not a possible explanation," said molecular immunologist David Weiner of the University of Pennsylvania, who was not involved in the research.
"Overall this is a positive and optimistic message for the field," said immunologist Dan Barouch, chief of Harvard University's Division of Vaccine Research and the lead author of one of the studies. "Other vaccine vectors can and should be further pursued in clinical trials."
Individuals who have previously been exposed to adenovirus serotype 5 (Ad5) -- a common cold virus -- have more Ad5-specific antibodies in their blood; that is, they are Ad5 seropositive. Analysis of the trial suggested that Ad5-seropositive subjects contracted HIV at a higher rate when they received the vaccine as opposed to the placebo. Researchers hypothesized that Ad5-seropositive individuals might be more sensitive to the Ad5 vector, and consequently, could "mount a more rapid, larger immune response," explained molecular biologist Alan Bernstein, executive director of Global HIV Vaccine Enterprise, who was not involved in the research. Because HIV attacks activated T cells, increased T-cell counts would provide more plentiful targets for HIV infection, and could thereby explain the boost in susceptibility.
The current studies analyzed frozen blood samples from two different precursor trials to the STEP study, and in both cases, the research teams disproved the idea that prior exposure to the Ad5 vector equated to higher T-cell counts. In the study led by Barouch, approximately 90% of subjects had Ad5-specific T cells prior to vaccination, but very few had Ad5-specific antibodies. This demonstrated that the two measures of immunity -- Ad5-specific antibodies and Ad5-specific T cells -- are not correlated, meaning that that Ad5 seropositivity cannot be used to predict levels of Ad5-specific T cells prior to vaccination.
(For the full story please visit www.The-Scientist.com)
