Vacc-4x: A Small Step Closer to a Therapeutic Vaccine?
A vaccine candidate designed to help treat HIV disease (rather than prevent infection) showed some promise in a small clinical trial, researchers report in the February 11, 2014, online edition of Lancet Infectious Diseases.
The trial evaluated the Vacc-4x vaccine candidate’s effect on CD4 cell counts during antiretroviral treatment interruptions and whether vaccinated participants could safely halt antiretroviral therapy (ART). Although vaccination yielded no benefit in these areas, Vacc-4x did provoke an immune response and was linked with lower viral load “set point” at the end of the treatment interruption period—which may help slow HIV disease progression.
“[T]he study reported here provides initial proof of concept to support a role for therapeutic HIV vaccines,” the authors write. “Therapeutic vaccines, such as Vacc-4x, might have a future role in complementing [ART] regimens, to improve or sustain HIV-specific immune responses and control viral load.”
Furthermore, they state, therapeutic vaccines may have role to play in producing a functional cure for HIV by reducing viral reservoirs, sources of “hidden” virus that is not actively replicating and therefore untouchable by current antiretroviral drugs.
What’s next for this particular therapeutic vaccine candidate? According to a press release from Bionor Pharma, maker of Vacc-4x, “33 patients from the trial are currently enrolled in the Company’s Phase II Vacc-4x Reboost trial which investigates whether, upon booster immunizations, the viral load can be reduced even further on a second treatment interruption. The trial expects to read out Q1 2014.”
For an in-depth look at the research results—and a discussion of ethical considerations for clinical trials involving treatment interruption—see Liz Highleyman’s summary, excerpted below and available in full at HIVandHepatitis.com.
February 20, 2014
By Liz Highleyman
An experimental therapeutic vaccine did not slow CD4 T-cell decline or enable study participants to safely interrupt antiretroviral therapy (ART) longer, but it did appear to leave HIV viral load at lower levels, researchers reported in the February 11 advance edition of Lancet Infectious Diseases.
Richard Pollard from UC Davis Medical Center and an international team of colleagues evaluated the safety, efficacy, and immunogenicity of Vacc-4x, a peptide-based therapeutic vaccine targeting conserved domains of HIV-1’s Gag p24 protein.
This Phase 2 study, conducted between July 2008 and June 2010, enrolled HIV positive adults at 18 sites in Germany, Italy, Spain, the U.K., and the U.S. The protocol initially called for 345 participants, but only 136 enrolled. At study entry participants were on combination antiretroviral therapy (ART) and had undetectable viral load (<50 copies/mL) and CD4 T-cell counts of at least 400 cells/mm3.
Participants were randomly assigned (2:1) to Vacc-4x or placebo arms, receiving weekly injections for 4 weeks followed by booster shots at weeks 16 and 18. At week 28, they underwent investigational ART interruption for up to 24 weeks. The primary endpoints were need for ART resumption and changes in CD4 counts during treatment interruption. Viral load, immunogenicity (as measured by ELISPOT and proliferation assays), and safety were also assessed….