January 16, 2015
Despite years of research and the success of science in preventing and elminating other diseases through immunization, a vaccine to prevent HIV remains elusive in large part because the virus targets exactly the cells that most vaccines use to create protection. In fact, vaccine-induced immune responses to HIV may actually make transmission more likely, according to recent research.
Two recent, large-scale clinical trials on vaccines found higher SIV acquisition in monkeys who were vaccinated compared to those who had received the placebo. A new primate study provides a simple explanation of this "backfire effect" -- increasing the number of immune cells also increases the number of targets for the virus.
T cells, a type of white blood cell, are one of the body's first lines of defense against intruders, such as bacteria and viruses. Two different types of T cells usually work together to fight off infections. CD4+ T cells are known as "helper" cells because they identify the infection, whereas CD8+ T cells have the job of killing the intruder. HIV specifically attacks CD4+ T cells and uses some of the information in those cells to replicate and spread throughout the body. For this reason, many vaccine attempts have also targeted CD4+ T cells but, as the new study suggests, activating too many of these cells is counterproductive.
Their results, published in the Proceedings of the National Academy of Sciences, found that immunization did not protect the animals against infection; however, monkeys who had been vaccinated had lower viral loads than those in the control group. Moreover, they found that even though the vaccinated monkeys had elevated levels of CD8+ T cells in their systems, these "killer" cells did not help prevent infection.
The most important finding, according to the authors, however, is "that the monkeys that became infected had higher levels of activated CD4+ T cells in rectal biopsies before challenge." This higher level of activated helper cells was associated with increased risk of breakthrough SIV infection in the vaccinated animals.
"This study shows that if a vaccine induces high levels of activated CD4+ T cells in mucosal tissues, any potential protective effect of the vaccine may be hampered," stated Guido Silvestri, one of the study authors.
Silvestri and colleagues also suggest that, "an effective T-cell-based AIDS vaccine should induce strong HIV-specific CD8+ T cells in mucosal tissues without increasing availability of target cells for the body."
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