Adenovirus antibodies assist HIV

Antibodies against a vaccine vector render T cells more susceptible to HIV-1 infection, say Perreau et al. on page 2717. Their results may help explain the failure of a recent HIV vaccine trial. The HIV-1 vaccine used in Merck's STEP trial relied on a weakened form of a common cold virus, Adenovirus 5 (Ad5), to carry bits of HIV into the body. One worry about the Ad5 vector was that widespread immunity to adenoviruses might cause the vaccine to be ousted before an anti-HIV response could develop. Instead, there was a chance that vaccine recipients who had circulating antibodies against Ad5 were contracting the virus more often, one factor that forced termination of the trial. Perreau et al. now show that HIV spread through T cell–dendritic cell (DC) co-cultures three times as fast when Ad5 and neutralizing antiserum—present in people with prior immunity—was added to the cultures. Ad5-antibody complexes triggered DC maturation in the presence of Fc␥ receptors (Fc␥R) and Toll-like receptor (TLR)–9. The authors suspect that Fc␥R facilitated the uptake of Ad5-antibody complexes into the cell, where viral components could then activate TLR9 to trigger DC maturation and activation. The mature DCs activated both CD4 + and CD8 + T cells, which may have assisted HIV infection in two ways. Activated CD4 + cells could provide HIV with more cells to infect. And activated Ad5-specifi c CD8 + T cells could attack infected DCs, thereby reducing the pool of DCs presenting HIV antigens. Indeed, weaker HIV-specifi c CD8 responses were seen in Ad5-seropositive individuals in response to vaccination. Merck's vaccine may have made it to phase 2 trials because nonhuman primates don't naturally come in contact with human adenoviruses, and therefore the potential problem went unrecognized. AM A popular epilepsy drug may also be benefi cial in patients with Alzheimer's disease (AD), if the fi ndings on page 2781 hold true in clinical trials. Qing et al. improved memory and ameliorated brain plaques in mice with an AD-like disease by injecting them with the anti-seizure drug valproic acid. Mice with the AD-like disease typically develop amyloid-rich brain plaques after six months. When Qing et al. treated the mice with valproic acid soon after plaque formation, the plaques shrank and some of the damaged axons in their brains resumed growth. The drug also improved performance in memory tests. The acid worked by inhibiting the activity of glycogen synthase kinase-3␤ (GSK-3␤), …