Herpes simplex virus binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

IgG possesses an important yet little recognized effector function in mucus: IgG bound to viral surface can immobilize otherwise readily diffusive viruses to the mucin matrix, excluding them from contacting target cells and facilitating their elimination by natural mucus clearance mechanisms. Cervicovaginal mucus (CVM) is populated by a microbial community, and its viscoelastic and barrier properties can vary substantially not only across the menstrual cycle but also in women with distinct microbiota. How these variations impact the “muco-trapping” effector function of IgGs remains poorly understood. Here, we obtained multiple fresh, undiluted CVM specimens (n=82 unique specimens) from six women over time, and employed high resolution multiple particle tracking to quantify the mobility of fluorescent Herpes Simplex Viruses (HSV-1) in CVM treated with different HSV-1-binding IgG. The IgG trapping potency was then correlated to the menstrual cycle and the vaginal microbial composition determined by 16s rRNA. In the specimens studied, both polyclonal and monoclonal HSV-1 binding IgG appeared to consistently and effectively trapped HSV-1 in CVM obtained at different times of the menstrual cycle and containing a diverse spectrum of commensals, including G. vaginalis-dominant microbiota. Our findings underscore the potential broad utility of this “muco-trapping” effector function of IgG to reinforce the vaginal mucosal defense, and motivates further investigation of passive immunization of the vagina as a strategy to protect against vaginally transmitted infections.