Re-boost immunizations with the peptide-based therapeutic HIV vaccine, Vacc-4x, restores geometric mean viral load set-point during treatment interruption.

BACKGROUND

Vacc-4x, a therapeutic HIV vaccine candidate has previously induced a significant reduction in viral load (VL) set-point compared to placebo upon interruption of combination anti-retroviral therapy (ART) (2007/1 study). This study, (2012/1), explored the potential to maintain Vacc-4x effect by re-boosting eligible 2007/1 study participants.

METHODS

Participant inclusion required 2007/1 participants to have completed all Vacc-4x immunizations and interrupted ART for up to 26 weeks. At weeks (wk)0 and 2, participants received intradermal (i.d.) Vacc-4x booster immunizations (1.2mg) on ART with GM-CSF (60μg) i.d. as a local adjuvant. ART was interrupted for up to 16 weeks (wk12-wk28). Participants were then followed on ART until wk36. VL set-point, total proviral DNA (pvDNA) and immunogenicity assessed by IFN-γ ELISPOT, T-cell proliferation and delayed type hypersensitivity (DTH) reactions were compared to participants' values in the 2007/1 study where available.

RESULTS

This open, multicenter, clinical study enrolled 33 participants from 9 clinical trial sites in the US and Europe. In the per-protocol (PP) population, the VL set-point geometric mean (GM) 18162 copies/mL was not significantly changed compared to the 2007/1 study (GM VL 22035 copies/mL), (p = 0.453, n = 18). For participants with available preART VL values, the VL set-point (GM 26279 copies/mL) remained significantly lower than the preART VL set-point (GM 74048 copies/mL, p = 0.021, n = 13). A statistically significant reduction in pvDNA (49%) from baseline to wk4 was observed (p = 0.03, n = 26). DTH responses (wk4) increased significantly from baseline (p = 0.006, n = 30) and compared to the 2007/1 study (p = 0.022, n = 29) whilst the proportion of participants with ELISPOT and T-cell proliferation responses was similar between the two studies.

CONCLUSIONS

Vacc-4x booster immunizations safely maintained the mean VL set-point at that established following primary Vacc-4x therapeutic immunization. The reduction in pvDNA during ART supports the potential for Vacc-4x immunization to reduce HIV reservoirs and thereby contribute to combination HIV cure strategies.

Déclaration de conflit d'intérêts

We have the following interests: This study was funded in part by the sponsor Bionor Immuno AS. During the course of the study Jürgen K Rockstroh, Giuseppe Pantaleo and Barry Peters were members of Bionor Immuno’s Clinical Advisory Board. Mats Ökvist (MO) and Maja A. Sommerfelt (MAS) were employees of Bionor Immuno and had shares in the company. Currently, MO and MAS are no longer employed at Bionor Immuno and do not have shares in the company. Darren Jolliffe (DJ) is employed by S-Cubed Biometrics Ltd., Kim Krogsgaard (KK) is employed by KLIFO. Neither S-Cubed nor KLIFO provided funding for the study. The remaining co-authors have no competing interests. The following patents related to this study are owned by Bionor Immuno AS: HIV PEPTIDES, ANTIGENS, VACCINE COMPOSITIONS, IMMUNOASSAYS KIT AND A METHOD OF DETECTING ANTIBODIES INDUCED BY HIV WO00/52040 and METHOD FOR REDUCING AND/OR DELAYING PATHOLOGICAL EFFECTS OF HUMAN IMMUNODEFICIENCY VIRUS I (HIV) OR FOR REDUCING THE RISK OF DEVELOPING ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) WO2016/005508. There are no further patents, products in development or marketed products to declare related to this study. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.