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Scott McKinley : Characterizing Antibody-Mucin Interactions That Produce a Dynamic Molecular Shield Against Viral Invasion

Given the difficulty in finding a cure for HIV/AIDS, a promising prevention
strategy to reduce HIV transmission is to directly block infection at the
portal of entry. The recent Thai RV144 vaccine trial offered the first
evidence that a vaccine may provide location protection and block HIV
transmission in the vagina. Unfortunately, the underlying mechanisms for
protection remain unclear. In this talk, we examine theoretically a
hypothesis that builds on Sam Lai's recent laboratory observation that
virus-specific antibodies (Ab) may be capable of trapping individual
virions in genital mucus secretions. Ab are known to have a weak –
previously considered inconsequential – binding affinity with the mucin
fibers that constitute cervicovaginal mucus (CVM). However, several Ab
may be bound to a single virion at the same time, multiplying the Ab-mucin
binding effect, thereby creating an indirect virion-mucin affinity. Our
model takes into account biologically relevant length and time scales,
while incorporating known HIV-Ab affinity and the respective diffusivities
of viruses and Ab in semen and CVM. The model predicts that HIV-specific
Ab in CVM can effectively immobilize HIV in a shock-like front near the
semen-CVM interface, far from the vaginal epithelium. The robustness of
the result implies that even weak Ab-mucin affinity can markedly reduce the
flux of virions reaching target cells. Beyond this specific application,
the model developed here is adaptable to other pathogens, mucosal barriers,
geometries, kinetic and diffusional effects, providing a tool for hypothesis
testing and producing quantitative insights into dynamics of immune-
mediated protection.

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