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

PLoS One. 2019 Jan 30;14(1):e0210965. doi: 10.1371/journal.pone.0210965. eCollection 2019.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01712256.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / adverse effects
  • Adult
  • Anti-HIV Agents / administration & dosage
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV Infections / virology*
  • Humans
  • Hypersensitivity, Delayed
  • Immunization Schedule
  • Immunization, Secondary / methods*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Viral Load* / drug effects
  • Viral Load* / immunology

Substances

  • AIDS Vaccines
  • Anti-HIV Agents
  • Vacc-4x

Associated data

  • ClinicalTrials.gov/NCT01712256

Grant support

This work was partly supported by grants from the Research Council of Norway GLOBVAC program (Project nr: 220762) and the tax incentive scheme SkatteFunn (Project nr: 224425). Remaining funding was provided by the Sponsor Bionor Immuno AS. The grant awarding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Mats Ökvist (MO) and Maja A. Sommerfelt (MAS) were employees of Bionor Immuno AS during the course of the study. Bionor Immuno AS sponsored the study and provided support in the form of salaries for authors MO and MAS. The specific roles of these authors are articulated in the ‘author contributions’ section. Bionor Immuno AS and its clinical advisory board were involved in the clinical trial design. Bionor Immuno AS was not involved in data collection and analysis, decision to publish, or preparation of the manuscript, but did approve the manuscript prior to submission. Darren Jolliffe (DJ) is employed by S-Cubed Biometrics Ltd. S-Cubed Biometrics Ltd. provided support in the form of salary for author DJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. Kim Krogsgaard (KK) is employed by KLIFO. KLIFO provided support in the form of salary for author KK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.