Vaccines designed to safeguard patients from HIV can
backfire and lead to increased rates of infection. This negative effect has
been seen in more than one vaccine clinical trial.
Scientists at the Yerkes National Primate Research Center,
Emory University, have newly published results that support a straightforward
explanation for the backfire effect. According to the study, the vaccination
may increase the number of immune cells that serve as viral targets.
In a nonhuman primate model of HIV transmission, higher
levels of viral target cells in gateway mucosal tissues were associated with an
increased risk of infection.
The findings suggest that vaccine researchers, when
evaluating potential HIV/AIDS vaccines, may need to steer away from those that
activate too many viral target cells in mucosal tissues.
"One of the reasons why it has been so difficult to
make an AIDS vaccine is that the virus infects the very cells of the immune
system that any vaccine is supposed to induce," says senior author Guido
Silvestri, chief of microbiology and immunology at Yerkes National Primate
A large part of the vaccine effort has been focused on
developing vaccines that stimulate antiviral T cells.
T cells come in two main categories, defined by the
molecules found on their surfaces.
CD8 is a marker for "killer" cells, while CD4 is a
marker for "helper" cells. CD4+ T cells are known to be primary
targets for HIV and SIV infection, while several studies have proposed that
CD8+ T cells could be valuable in controlling infection.
"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," he explains.
The study emphasizes the unique challenges that HIV poses in
terms of vaccine development, and the importance of pursuing vaccine concepts
and products that elicit strong antiviral immune responses without increasing
the number of CD4+ T cells in the