Engineering monoclonal antibody-based contraception and multipurpose prevention technologies†

Abstract

<jats:title>Abstract</jats:title> <jats:p>Sexually transmitted infections are highly prevalent, and over 40% of pregnancies are unplanned. We are producing new antibody-based multipurpose prevention technology products to address these problems and fill an unmet need in female reproductive health. We used a Nicotiana platform to manufacture monoclonal antibodies against two prevalent sexually transmitted pathogens, HIV-1 and HSV-2, and incorporated them into a vaginal film (MB66) for preclinical and Phase 1 clinical testing. These tests are now complete and indicate that MB66 is effective and safe in women. We are now developing an antisperm monoclonal antibody to add contraceptive efficacy to this product. The antisperm antibody, H6-3C4, originally isolated by Shinzo Isojima from the blood of an infertile woman, recognizes a carbohydrate epitope on CD52g, a glycosylphosphatidylinositol-anchored glycoprotein found in abundance on the surface of human sperm. We engineered the antibody for production in Nicotiana; the new antibody which we call “human contraception antibody,” effectively agglutinates sperm at concentrations &amp;gt;10 μg/ml and maintains activity under a variety of physiological conditions. We are currently seeking regulatory approval for a Phase 1 clinical trial, which will include safety and “proof of principle” efficacy endpoints. Concurrently, we are working with new antibody production platforms to bring the costs down, innovative antibody designs that may produce more effective second-generation antibodies, and delivery systems to provide extended protection.</jats:p>

Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial

“…Further research is required to determine if more than 1 anti-HIV antibody is needed for optimal efficacy and to avoid HIV escape mutations. Thus, additional mAbs against HIV-1 and other STI pathogens, as well as contraceptive mAbs [ 53 ], could be included in an eventual commercial mAb-MPT product to provide more comprehensive protection.…”

Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy

“…However, in this phase 1 clinical study, there is variability in film dissolution rate, which will influence changes in release kinetics, and PK testing was not conducted between days 1 through 7 [ 45 ]; therefore, further testing is required for this formulation. Nevertheless, due to the promising inhibitory effects of MB66, Anderson et al suggested utilizing “human contraceptive antibody” (HCA) for an MPT vaginal film for HIV, HSV, and contraception [ 103 ]. HCA is the only antisperm antibody in advanced development and shown to promote sperm agglutination, trap flagellating sperm in human midcycle cervical mucus (mucus trapping), and promote viral neutralization of HIV and HSV [ 103 ].…”

Emerging antibody-based products for infectious diseases: Planning for metric ton manufacturing

“…In addition to manufacturing scale requirements, cost is a clear constraint for such a product. We estimate that COGs for a dose would need to be no more than $0.25, 44 translating to $6.25 per gram, a goal not yet achieved by existing manufacturing platforms.…”

“…Prevention of vaginal transmission of HIV and HSV coupled with a contraceptive antibody has been discussed above. 42,44 There are more than 10 mAbs in preclinical or early stage clinical development for enteric diseases 2 that may be amenable to oral delivery. In the respiratory tract, the limited bioavailability of systemically delivered IgG in tissues affected by the disease, especially the lungs, may be limiting the efficacy of mAbs for diseases such as RSV, influenza and SARS-CoV-2.…”