Towards Eradication of HIV-1: Therapeutic Vaccination with the peptide-based candidate Vacc-4x

The Vacc-4x Reboost study (NCT01712256) followed on from the large Phase II clinical study (NCT00659789) where the peptide-based therapeutic HIV vaccine candidate, Vacc-4x, induced a statistically significant reduction in viral load set-point compared to placebo following interruption of antiretroviral therapy (ART) lasting up to 6 months. The viral load set-point is a measure of where, on average, the viral load level stabilizes if ART is interrupted. Participants that had been immunized with Vacc-4x provided a unique opportunity to determine whether the viral load set-point achieved in the large phase II clinical study could be reduced even further if participants were given new booster immunizations with Vacc-4x. Thirty-three participants from nine of the participating clinical trial sites (USA, Germany, Italy, UK and Spain) provided informed consent to participate in this ReBoost study. The immunization schedule consisted of two booster Vacc-4x immunizations while on ART using granulocyte-macrophage colony stimulating factor (GM-CSF) as a local adjuvant as in all previous Vacc-4x clinical studies. Study volunteers remained on ART, for 10 weeks prior to treatment interruption for up to 16-weeks. Following their return to ART, participants were followed for another 8 weeks. Three of the participants, however, had not resumed ART after the previous large Phase II study and carried out the entire ReBoost study while off ART. Enrolment was completed in April 2013 and the study concluded in January 2014. The clinical study report were completed in December 2014. Re-immunization (ReBoosting) with Vacc-4x was found to be safe and well tolerated. The viral load set-point in the ReBoost study was lower than that achieved in the previous phase II clinical study, but not statistically significantly so. The findings nevertheless showed that Vacc-4x immunization had fundamentally changed the response to HIV because the viral load set point remained lower than the level participants had when they first started ART, and after the first placebo-controlled clinical study. It also showed that reBoosting was safe and effective, and could be used to maintain reductions in viral load set-point. Furthermore, this study also showed a statistically significant reduction in HIV reservoirs in blood, an important measure in clinical studies aimed at achieving a functional HIV cure. Vacc-4x has since been shown to reduce HIV reservoirs in the REDUC clinical study partly supported by GLOBVAC (Project no: 235955) The second part of this project was to carry out the GM-CSF study. Completing this study is a requirement from the FDA to enable Vacc-4x development to progress to clinical phase III. Due to a number of re-organizations of management in the company since January 2015, the planned GM-CSF clinical study has not been performed. Recently, Bionor?s new owners elected to wind down company activities whilst they continue to actively look for a new entity that may take over the Bionor technology.

Human immunodeficiency virus (HIV)-1 infection continues to threaten global health with approximately 34 million adults and children living with HIV infection worldwide in 2010. Antiretroviral therapy (ART) has made a significant impact on HIV infection, however, since it cannot eradicate HIV, ART must be taken daily for life, thereby conferring a significant financial burden on healthcare services worldwide. Evidence of HIV eradication in a single subject (the Berlin Patient) has fueled interest in deve loping a cure for HIV infection. Vacc-4x, a peptide-based therapeutic HIV vaccine has recently shown a statistically significant reduction in viral load on treatment interruption in a phase II clinical study partly supported by GLOBVAC (project nr 192538) . The present study aims to determine the potential for re-boosting subjects from the phase II study to see if viral load can be reduced even further on a second treatment interruption. This study will provide important proof-of-concept data regarding the feasibility of successive treatment interruptions supported by therapeutic vaccination leading to successive reductions in viral load and ultimately HIV eradication. This study will also determine the contribution of granulocyte macrophage colony stimul ating factor (GM-CSF) as a local adjuvant (catalyzing immune responses to Vacc-4x). HIV positive subjects will be immunized in the presence or absence of GM-CSF respectively while on ART, also using a needle-free injection device to improve accuracy and t o facilitate delivery in a mass immunization setting. This study was a requirement from the FDA to allow Vacc-4x to reach end-of-phase II and progress to the next stage of clinical development (phase III).