Fig 1. A visualization of the four different mechanisms of action of the anti-α4β7 antibody and corresponding model diagram.
A) Model schematic in the absence of the anti-α4β7 antibody. Target cells (T) proliferate logistically at rate rT, die at rate dT and become infected at rate (1- ε)V, where β is the transmission rate, ε is the efficacy of cART, and V is the viral concentration. Once target cells are infected, a fraction f become latent cells (L) and the remaining become productively infected cells (I). Latent cells proliferate at rate rL, die at rate dL, and activate at rate α. Infected cells produce virus at rate p, die due to viral cytopathic effects at rate δ, and are killed at rate mE by effector cells (E). Effector cells are produced at rate λE, proliferate at a maximum rate bE, become exhausted at a maximum rate dE, and die at rate μ. Virus is cleared in the absence of the anti-α4β7 antibody at rate c. B) Increased viral clearance. The anti-α4β7 monoclonal antibody (purple) (AB) binds to α4β7 integrin (red and blue) expressed on the viral membrane and opsonizes the virus, increasing the clearance rate γ-fold or less depending on the AB concentration. C) Viral neutralization. The anti-α4β7 monoclonal antibody (purple) binds to the α4β7 integrin (red and blue) expressed on the viral membrane, causing increased viral clearance and viral neutralization, i.e. inhibition of infection, while also contributing to increased viral clearance. D) Protection from infection. The anti-α4β7 monoclonal antibody binds to α4β7 integrin expressed on the surface of uninfected CD4+ T cells and protects them from infection. Target cells enter a protected state (P) at a maximum rate ρ, with protection waning at a maximum rate ⍵. E) Increased antigen presentation. Antibody-virus complexes are picked up by antigen presenting cells resulting in increased antigen presentation. We assume that this increased antigen presentation increases the effector cell source rate dependent on the AB concentration and the parameter Ω. The formation of antibody-virus complexes may also contribute to increased viral clearance.