Fast dissolving antibody tablets for preventing vaginal HSV transmission

Project Summary Despite immense efforts in educational and behavioral interventions to promote safer sexual practices, sexually transmitted infections (STIs) such as genital herpes remain highly prevalent, with an estimated 12% of people age 14-49 infected with HSV-2 in the United States. Unfortunately, there are no effective vaccines or microbicides for the majority of STIs, including HSV. An on-demand, fast-acting, safe, effective, and discreet vaginal microbicide would provide a powerful prevention tool to address gaps not addressed by behavioral and current pharmacologic interventions. Human monoclonal antibodies (mAb) delivered locally to mucosal surfaces offer exceptional promise, combining a long history of safety, anti-viral effectiveness, and unparalleled target specificity. Mucommune has been pioneering mAb technologies designed for mucosal applications, including muco-trapping mAbs that neutralizes and physically traps individual pathogens in mucus, based on carefully-tuned affinity between IgG-Fc and mucins. These “muco-trapping” mAbs can fully trap HSV particles in human cervicovaginal mucus (CVM) across the menstrual cycle and in CVM from women with diverse vaginal microflora, with ~10-fold greater potency than protection by neutralization alone. More importantly, trapping viruses in mucus with vaginally-dosed mAbs directly blocked transmission in a mouse vaginal Herpes model, in the absence of other immune protective functions. In this Phase I SBIR, we will build upon our work to formulate our pathogen-trapping mAb into fast dissolving Ab tablets (FDATs), which will rapidly disintegrate and disburse upon contact with CVM, providing rapid and potent immunoprotection. In Aim 1, we will incorporate muco-trapping mAbs against HSV into various FDAT formulations containing different types/ratios of excipients, binders and disintegrants. We will characterize the physical properties of the FDATs, measure the dissolution rates of FDATs in synthetic mucus and mixtures of fresh human CVM/semen, as well as verify the binding affinity of the mAb pre- post- FDAT formulation and dissolution. In Aim 2, we will evaluate our lead FDAT formulations from Aim 1 in a sheep vagina model to verify FDAT disintegration times, mAb pharmacokinetics and biodistribution, pharmacodynamics, and safety. Successful completion of these studies will enable us to identify a suitable FDAT formulation to advance into IND-enabling preclinical and clinical development, and provide the essential data for a Phase II proposal supporting development of shelf-stable FDAT that includes mAb cocktail consisting of both anti-HSV mAb and our lead contraceptive mAb (MM008), providing effective multipurpose protection against both vaginal Herpes transmission and pregnancy.