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… 
α4β7high CD4+ T cells are prone to be infected by HIV‐1 and associated with HIV‐1 disease progression
To investigate the characteristics of β7high CD4+ T cells during HIV‐1 infection and the relationship between β7 high T cells and HIV‐ 1 disease progress, a large number of subjects were randomly selected to undergo cell reprograming.
Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques
  • W. Ziani, Jiasheng Shao, Huanbin Xu
  • Biology, 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.
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.
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.
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.
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.
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.


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.
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.
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.
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.
Integrin alpha(4)beta(7) expression on peripheral blood CD4(+) T cells predicts HIV acquisition and disease progression outcomes
It is shown that pre-HIV infection levels of α 4 β 7+ 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 this association was stronger when infection was caused by HIV strains containing V2 Env motifs with a preference for β 7 binding.
Structural specializations of \(\alpha_4 \beta_7\), an integrin that mediates rolling adhesion
Lack of induction of the open headpiece conformation by ligand binding enables rolling adhesion to persist until integrin activation is signaled.
Early treatment of SIV plus macaques with an alpha(4)beta(7) mAb alters virus distribution and preserves CD4(+) T cells in later stages of infection
It is determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary and inguinal lymph-nodes in rhesus macaques infected with SIV.
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.
Expression and function of alpha 4/beta 7 integrin on human natural killer cells.
The results indicate that upon IL-2-activation, expression of functional alpha 4 beta-integrin is induced on NK cells potentially participating in their interaction with both extracellular matrix and endothelial cells.