Vedolizumab-mediated integrin α4β7 blockade does not control HIV-1SF162 rebound after combination antiretroviral therapy interruption in humanized mice.

  title={Vedolizumab-mediated integrin $\alpha$4$\beta$7 blockade does not control HIV-1SF162 rebound after combination antiretroviral therapy interruption in humanized mice.},
  author={Lijun Ling and Tongjin Wu and Kelvin Kai-Wang To and Ka-wai Cheung and Kathy Oi Lan Lui and Mengyue Niu and Ka Shing Lam and Chi Chi Wang and Jiatao Li and Hui Wang and Kwok Yung Yuen and Zhiwei Chen},
  volume={33 4},
OBJECTIVE The combined combination antiretroviral therapy (cART) and anti-α4β7 RM-Act-1 antibody therapy allows macaques to durably control simian immunodeficiency virus (SIV) rebound after withdrawal of the interventions. Here, we aimed to investigate whether vedolizumab (VDZ), a clinical-grade humanized anti-α4β7 antibody, would have similar effects in controlling live HIV-1 infection in humanized mice. DESIGN AND METHODS The integrin α4β7 blockade by VDZ was evaluated on human primary… Expand
Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
  • W. Ziani, Jiasheng Shao, +4 authors Huanbin Xu
  • Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2021
The findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV‐1/SIV infection. Expand
Integrin α4β7 in HIV‐1 infection: A critical review
The jury is still out on the role of α4β7 in HIV‐1 infection, and conflicting results have been reported on the effects of the same antibody, in combination with ART, during the early chronic phase of SIV infection. Expand
Search for antiviral functions of potentially protective antibodies against V2 region of HIV-1
  • M. Gorny
  • Medicine
  • 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. Expand
Anti-trafficking agents in the treatment of inflammatory bowel disease.
A class of therapeutics with growing importance in the field of inflammatory bowel diseases that specifically inhibit steps of immune cell trafficking that can be considered an indispensable column of IBD therapy is described. Expand
Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis
The results of the current study will contribute to the understanding of the dynamics of α4β7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy. Expand
Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
Assessment of V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features found lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs. Expand
Vedolizumab use and the associations between α4β7 expression and HIV reservoir in the gut during treated primary HIV infection.
Results from two multicentre, double-blind, randomised, noninferiority, phase 3 trials on the use of antiretroviral drugs for treatment and prevention of HIV infection in adults in adults aged 50 years or older in Spain are published. Expand


Cryptopatches are essential for the development of human GALT.
A human-mouse chimeric model characterized by the development of human GALT structures originating in mouse cryptopatches is bioengineered, which represents the most comprehensive experimental platform currently available for the study and for the preclinical testing of therapeutics designed to repair disease-damaged GALT. Expand
Brain Invasion by CD4+ T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice
The establishment of two useful NSG-HuPBL models are indicated, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. Expand
In vitro assessment of the effects of vedolizumab binding on peripheral blood lymphocytes
In vitro assays with human peripheral blood lymphocytes demonstrated that VDZ fails to elicit cytotoxicity, lymphocyte activation, and cytokine production from memory T lymphocytes and does not interfere with the suppressive ability of regulatory T cells, and insight into the mechanisms underlying the observed safety profile of VDz in clinical trials is provided. Expand
Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice
The results warrant the clinical development of BiIA-SG as a promising bs-bnAb–based biomedical intervention for the prevention and treatment of HIV-1 infection. Expand
α4β7+ CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection
It is suggested that the TGF-β-dependent TEM-to-TCM differentiation is a previously unrecognized mechanism for the formation of latently infected TCM after HIV-1 infection. Expand
AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice
Surprisingly, the prolonged in vivo expression of AAV-vectored hFlt3L resulted in significant suppression of total human CD34+ cell engraftment and differentiation, which was likely associated with the induction of murine myeloid-derived immune suppressive cells and reactive oxygen species in NSG-huCD34 mice. Expand
Integrin alpha4beta7 expression on peripheral blood CD4(R) T cells predicts HIV acquisition and disease progression outcomes
  • Sci Transl Med
  • 2018
Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques
New insights are provided into the mechanisms by which Rh-α4β7 may mediate its effect in SIV-infected macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease. Expand
The role of integrin alpha4beta7 in HIV pathogenesis and treatment
  • Curr HIV/AIDS Rep
  • 2018
Sustained virologic control in SIV+ macaques after antiretroviral and alpha(4)beta(7) antibody therapy
This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy, and develops a recombinant rhesus monoclonal antibody against the heterodimeric form of α4β7 (α4β 7 mAb) that blocks α4 β7 binding to MAdCAM. Expand