Open AccessAnti-α 4 β 7 monoclonal antibody–conjugated nanoparticles block integrin α 4 β 7 on intravaginal T cells in rhesus macaques
Author(s) -
Sidi Yang,
Géraldine Arrode-Brusés,
Ines Frank,
Brooke Grasperge,
James Blanchard,
Agegnehu Gettie,
Elena Martinelli,
Emmanuel A. Ho
Publication year - 2020
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abb9853
Subject(s) - monoclonal antibody , simian immunodeficiency virus , rhesus macaque , antibody , macaque , virology , systemic administration , monoclonal , immunology , biology , virus , microbiology and biotechnology , chemistry , paleontology , in vivo
Intravenous administration of anti-α 4 β 7 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 4 β 7 antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α 4 β 7 monoclonal antibody-conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α 4 β 7 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 α 4 β 7 , and occupied ~40% of α 4 β 7 expressed by these subsets and ~25% of all cells expressing α 4 β 7 Blocking of the α 4 β 7 was restricted to the vaginal tract without any changes detected systemically.