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


ABSTRACT: Intravenous administration of anti-α4β7 monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-α4β7 antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α4β7 monoclonal antibody-conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α4β7 gel). When intravaginally administered as a single dose in a rhesus macaque model, the formulation preferentially bound to CD4+ or CD3+ T cells expressing high levels of α4β7, and occupied ~40% of α4β7 expressed by these subsets and ~25% of all cells expressing α4β7 Blocking of the α4β7 was restricted to the vaginal tract without any changes detected systemically.

SUBMITTER: Yang S 

PROVIDER: S-EPMC7442472 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Anti-α<sub>4</sub>β<sub>7</sub> monoclonal antibody-conjugated nanoparticles block integrin α<sub>4</sub>β<sub>7</sub> on intravaginal T cells in rhesus macaques.

Yang Sidi S   Arrode-Bruses Geraldine G   Frank Ines I   Grasperge Brooke B   Blanchard James J   Gettie Agegnehu A   Martinelli Elena E   Ho Emmanuel A EA  

Science advances 20200821 34


Intravenous administration of anti-α<sub>4</sub>β<sub>7</sub> monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-α<sub>4</sub>β<sub>7</sub> antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α<sub>4</sub>β<sub>7</sub> monoclona  ...[more]

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