A therapeutic vaccine candidate briefly controls viral load
A team of researchers from Spain reported last month that a therapeutic AIDS vaccine candidate allowed some HIV-infected individuals freedom from the daily grind of combination antiretroviral therapy (cART), though the reprieve was short-lived. Findings from the Phase 1 trial, which were published in the Jan. 2 issue of Science Translational Medicine, are the latest from a burgeoning field of HIV research that seeks to control HIV replication without cART—known in the scientific shorthand as a “functional cure.”
To make the vaccine candidate, researchers extracted a subset of dendritic cells (DCs)—which patrol the body for invading pathogens and “show” them to other soldiers of the immune response—along with HIV from the blood of 36 HIV-infected individuals on cART. They inactivated the HIV in 22 of the 36 samples with heat, and then vaccinated the 22 individuals three times over a six-week period with high doses of their own DCs and the inactivated HIV. The other 14 HIV-infected individuals received three doses of their DCs with their own intact HIV. The immunizations were given either before or immediately after interruption of cART.
Twelve weeks following treatment interruption, researchers observed a 90% decrease in baseline viral load among 12 HIV-infected participants who received DC cells pulsed with the inactivated HIV, compared to just one in the control arm. By week 24, seven participants randomized to the DC-inactivated HIV arm maintained this dramatic drop in baseline viral load, while none did in the control arm. The significant decrease in plasma viral load observed in the immunized individuals corresponded with a consistent increase in HIV-specific T-cell responses, the authors of the study noted.
Unfortunately, by week 48 the virus had rebounded in all trial participants, ruling out the tantalizing possibility that this intervention might have been able to achieve a functional cure in some individuals. “The goal of any therapeutic vaccine would be to control viral replication to an undetectable level in at least a proportion of patients in the absence of combination antiretroviral therapy, and this objective has not been reached with this vaccine,” researchers noted in the study.
Nonetheless, University of Barcelona scientist Felipe García, the lead author of the study, said this is the first randomized, placebo-controlled study of a therapeutic vaccine candidate that shows a statistically significant trend downward in viral load. “This is the most important message—that it is possible to change the viral load set point by inducing new immune responses in the body.”
Dendritic cells operate like a 24-hour security force, roaming the body looking for foreign invaders. Once they come in contact with viruses, they grab hold of enemy infiltrators with finger-like projections, swallow them whole and present their fragments to T cells, to inform the immune system about the attack (see VAX Dec. 2008 Primer on Understanding Innate Immunity and HIV). But in HIV infection, dendritic cells can also carry live virus to CD4+ T cells, and their interactions with T cells can backfire, driving the infection rather than thwarting it. But the Spanish researchers hypothesized that by combining DCs and heat-inactivated HIV in a vaccine candidate, they might prompt the body to mount cellular immune responses against the live virus circulating in the body. This seems to have worked to a degree in this study, though not well enough to keep the HIV-infected individuals off cART for very long.