Successful therapeutic vaccination of HIV patients with Vacc-4x, Bionor Pharma’s peptide-based therapeutic vaccine for HIV-1 infection
Bionor Pharma announced today presentation of data from its international multicenter double-blinded placebo-controlled phase IIB study at the IAS conference in Rome. As previously communicated, a statistically significant difference in viral load set point was observed between the Vacc-4x and placebo arms at the end of the study period (p=0.002). Further post-hoc analyses for patients with preART VL values and who remained off ART for 6 months, showed a statistically significant reduction in VL from their preART level (0.55 log, p=0.0003) in the Vacc-4x group at the end of the study period compared to a non-statistically significant VL reduction (0.08 log, p=0.89) in the placebo group. Furthermore, the viral load of immune response (ELISPOT) positive Vacc-4x subjects was significantly lower than that of ELISPOT positive subjects in the placebo group (p=0.023) (Wilcoxon Mann-Whitney) indicating that Vacc-4x immunization may improve immune responses to p24 leading to a lower viral load set point. These findings warrant further investigation in future clinical trials.
(Oslo, July 18th 2011) Bionor Pharma ASA presents today for the first time at an international scientific conference, the initial findings from its international (USA, UK, Germany, Italy, Spain) multi-center randomized placebo-controlled phase IIb study of Vacc-4x, the company’s most advanced HIV-vaccine candidate. Vacc-4x is designed to target immune responses to conserved domains of p24 since sustained immune responses to p24 have been shown to be associated with delayed disease progression. Conserved domains are shared between diverse strains and are immunologically vulnerable. The IIb clinical study is presented as a poster at the International AIDS Society (IAS) Conference on HIV Pathogenesis Treatment and Prevention in Rome 17-20th July. The main conclusions on primary and secondary endpoints have been reported in earlier press releases. Although no difference was observed in time to return to ART, or in CD4 counts over time between the Vacc-4x and placebo groups, the data showed a statistically significanttreatment difference in plasma viral load set point between the Vacc-4x and placebo groups (p=0.002). There was also a statistically significantdifference in viral load set point (mean of weeks 48 & 52) compared to preART values in the Vacc-4x, but not the placebo group. Furthermore preliminary immunological analyses show that positive ELISPOT responses to p24 in the Vacc-4x group were associated with a reduced viral load set point compared to placebo. This indicates a potential qualitative rather than a quantitative difference in immunological responses to p24 between Vacc-4x and placebo groups.
Positive ELISPOT responses to p24 in the Vacc-4x group were associated with a reduced viral load set point compared to placebo group, indicating that Vacc-4x immunization may improve immune responses to p24 leading to a lower viral load set point. Interestingly, a recent independent publication has highlighted a number of conserved sectors on p24 as immunologically vulnerable and where immune escape results in defective virus. Vacc-4x largely corresponds to two of these sectors.
Further immunological analyses are ongoing to characterize the differences in immune responses to p24 between the Vacc-4x and placebo groups using different immunological techniques. These extended immunological analyses will be presented at a later date.
“The immunological analysis presented here supports the viral load findings reported earlier”. says CEO Henrik Lund. “We are currently in the process of planning further clinical trials.”
“The findings in this study show that patients that are well controlled on ART and having a well-functioning immune system, may benefit from therapeutic immunization”. says Prof. Jürgen Rockstroh, University of Bonn, Germany. “It looks like a combination of ART and therapeutic vaccines could be the way to go.”
“The recent publication from Proceedings of the National Academy of Sciences, USA highlighting regions on p24 that cannot be changed without affecting viral fitness and that Vacc-4x is also derived from such conserved regions on p24, makes these findings highly interesting”, says Prof. Rich Pollard, University of California, Davis, USA.
ART = Anti-Retroviral Therapy
pre-ART viral load = viral load prior to initiation of ART
ELISPOT = Enzyme Linked Immuno-Spot Assay for quantification of specific T-cell responses
Qualitative vs. Quantitative immune response = a Qualitative immune response is associated with an effect on viral load in contrast to a Quantitative response.
Proceedings of the National Academy of Sciences, USA: Dahirel V. et al. 2011. Coordinate linkage of HIV evolution reveals regions of immunological vulnerability. www.pnas.org/cgi/doi/10.1073/pnas.1105315108