An open-label phase 1 clinical trial of the anti-α4β7 monoclonal antibody vedolizumab in HIV-infected individuals

  title={An open-label phase 1 clinical trial of the anti-$\alpha$4$\beta$7 monoclonal antibody vedolizumab in HIV-infected individuals},
  author={Michael C. Sneller and Katherine E. Clarridge and Catherine A Seamon and Victoria Shi and Marek Dominick Zorawski and Jesse S. Justement and Jana Blazkova and Erin Huiting and Michael A. Proschan and Jorge Rodrigo Mora and Michael Shetzline and Susan Moir and Henry Clifford Lane and Tae-Wook Chun and Anthony S. Fauci},
  journal={Science Translational Medicine},
Infusions of anti-α4β7 monoclonal antibody did not affect plasma viral rebound in HIV-infected individuals who stopped antiretroviral drug therapy. Targeting α4β7 in HIV Nonhuman primate models can be useful in the development of new approaches to treating HIV infection. Sneller et al. conducted a human therapeutic trial based on promising results of a single nonhuman primate study in which treatment with an anti-integrin monoclonal antibody led to sustained suppression of SIV plasma viremia… 

Combination therapies currently under investigation in phase I and phase II clinical trials for HIV-1

This report provides a review of investigational drugs and cell-based interventions against HIV infection that are currently under Phase I or Phase II clinical trials, and reports on new antiretroviral drugs, antibodies directed against viral or host targets, reactivating agents, immune modulators and immune checkpoint inhibitors, andcells tested in combination.

Vedolizumab treatment across antiretroviral treatment interruption in chronic HIV infection: the HAVARTI protocol for a pilot dose-ranging clinical trial to assess safety, tolerance, immunological and virological activity

This study proposes to assess the safety and tolerability of vedolizumab, a licensed humanised mAb against human α4β7 integrin, in healthy HIV-infected adults on ART and assess, by analytical treatment interruption (ATI), whether vEDolizUMab treatment can induce SVR beyond ART and vedOLizumAB treatment.

Search for antiviral functions of potentially protective antibodies against V2 region of HIV-1

  • M. Gorny
  • Biology
    Human vaccines & immunotherapeutics
  • 2020
Observations suggest that V2 Abs may not control SHIV infection in rhesus macaques and that V 2 Abs may instead be a surrogate marker of other protective immune responses.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial

The prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells and presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption.

Novel therapeutic approaches for treatment of COVID-19

The therapeutic approaches that are used to treat the coronavirus disease of 2019 have been summarized and there is no doubt that more studies are required to clarify immunopathogenesis and immune response; however, new therapeutic approaches including mesenchymal stromal cell and immune cell therapy showed inspiring results.

Anti-α4β7 monoclonal antibody–conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques

A novel intravaginal formulation consisting of anti-α4β7 monoclonal antibody–conjugated nanoparticles loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α 4β7 gel) that blocks integrin α4 β7 on intravagsinal T cells in rhesus macaques reduces simian immunodeficiency virus infection and reduces gut SIV loads.

The Hitchhiker Guide to CD4+ T-Cell Depletion in Lentiviral Infection. A Critical Review of the Dynamics of the CD4+ T Cells in SIV and HIV Infection

New therapeutic strategies limiting mucosal pathology, microbial translocation and IA/INFL, to improve CD4+ T-cell recovery and the overall HIV prognosis are needed, and SIV models are extensively used to this goal.

HIV-1 acquisition in a man with ulcerative colitis on anti-α4β7 mAb vedolizumab treatment.

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism, and the impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease.



Lack of therapeutic efficacy of an antibody to α4β7 in SIVmac251-infected rhesus macaques

It is demonstrated that anti-α4β7 antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques, and three new studies found that treating with the antibody had any effect on virologic control after stopping ART treatment.

Evaluation of an antibody to α4β7 in the control of SIVmac239-nef-stop infection

Three new studies found that treating with the antibody had any effect on virologic control after stopping ART treatment, and it was found that anti-α4β7 treatment did not have a detectable impact on plasma viremia, tissue viral load, or CD4+ T cell counts.

Blocking α4β7 integrin binding to SIV does not improve virologic control

Three new studies found that treating with the antibody had any effect on virologic control after stopping ART treatment, and compared this treatment to treatment with non-neutralizing monoclonal antibodies against the SIV envelope glycoprotein that only block α4β7 binding to SIV Env but have no other host-directed effects.

Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy

Combining short-term antiretroviral therapy with specific anti-integrin treatment sustains low viral loads in monkeys and allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy.

A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection

The results suggest that any future HIV intervention trials would benefit from the inclusion of a placebo arm, and the degree and kinetics of plasma viral rebound after ART interruption have potentially important implications for the design of future interventions aimed at achieving ART-free control of HIV infection.

Preliminary in vivo efficacy studies of a recombinant rhesus anti-α 4 β 7 monoclonal antibody 1

Characterization of α 4 β 7 expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T- cells, but high densities were observed on TCM (central memory] T-cells.

HIV reservoirs: pathogenesis and obstacles to viral eradication and cure

The pathophysiology of CD4+ T-cell HIV reservoirs is discussed, including recent advances in the understanding of the mechanisms of persistent viral infection and perspectives for eradication of HIV in infected individuals.

Antiretroviral therapy and management of HIV infection

Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes

This study shows that pre-HIV infection frequencies of α4β7+ peripheral blood CD4+ T cells, independent of other T cell phenotypes and genital inflammation, were associated with increased rates of HIV acquisition in South African women and supported further evaluation of targeting α4 β7 integrin as a clinical intervention during HIV infection.

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis and the frequency of adverse events was similar in the vedolIZumab and placebo groups.