Fast dissolving antibody tablets for preventing vaginal HSV transmission

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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.