ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study

Thurman, Andrea Ries; Moench, Thomas R.; Hoke, Marshall; Politch, Joseph A.; Cabral, Howard; Mausser, Emilie; Nador, Ellena; Morton, Josh; Hamorsky, Krystal Teasley; Swope, Kelsi; Bratcher, Barry; Anderson, Deborah J.; Whaley, Kevin J.

doi:10.1016/j.ajog.2023.02.024

Cited by 11 publications

(8 citation statements)

References 58 publications

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“…A recently completed phase 1 clinical trial of ZB-06, a vaginal film containing HCA, suggested that certain HCA Fc functions are important for contraception [ 23 ]. Notably, HCA mediates CDC [ 16 ], and high numbers of immotile sperm in cervical mucus in women using the ZB-06 film suggest that CDC may be an important contraceptive effect.…”

Section: Discussionmentioning

confidence: 99%

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Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody

Nador,

Xia,

Santangelo

et al. 2024

Antibodies

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IgG Fc N-glycosylation is necessary for effector functions and is an important component of quality control. The choice of antibody manufacturing platform has the potential to significantly influence the Fc glycans of an antibody and consequently alter their activity and clinical profile. The Human Contraception Antibody (HCA) is an IgG1 antisperm monoclonal antibody (mAb) currently in clinical development as a novel, non-hormonal contraceptive. Part of its development is selecting a suitable expression platform to manufacture HCA for use in the female reproductive tract. Here, we compared the Fc glycosylation of HCA produced in two novel mAb manufacturing platforms, namely transgenic tobacco plants (Nicotiana benthamiana; HCA-N) and mRNA-mediated expression in human vaginal cells (HCAmRNA). The Fc N-glycan profiles of the two HCA products were determined using mass spectrometry. Major differences in site occupancy, glycan types, and glycoform distributions were revealed. To address how these differences affect Fc function, antibody-dependent cellular phagocytosis (ADCP) assays were performed. The level of sperm phagocytosis was significantly lower in the presence of HCA-N than HCAmRNA. This study provides evidence that the two HCA manufacturing platforms produce functionally distinct HCAs; this information could be useful for the selection of an optimal platform for HCA clinical development and for mAbs in general.

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Section: Discussionmentioning

confidence: 99%

“…Because the Nicotiana plants used in this system are transgenic strains with altered glycosylation pathways, the expressed antibodies contain mammalian glycoforms. This production method is currently being used to manufacture HCA-formulated topical vaginal films for clinical trials [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody

Nador,

Xia,

Santangelo

et al. 2024

Antibodies

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“…One non-barrier product under the clinical trial is ZB-06 vaginal film [213]. ZB-06 contains a monoclonal antibody (mAb) against CD52g that effectively acts as a sperm-immobilizing agent [214].…”

Section: Non-hormonal Methodsmentioning

confidence: 99%

Reversible female contraceptives: historical, current, and future perspectives

Barton,

Erickson,

Allred

et al. 2023

Biology of Reproduction

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Contraception is a practice with extensive and complicated social and scientific histories. From cycle tracking, to the very first prescription contraceptive pill, to now having over-the-counter contraceptives on demand, family planning is an aspect of healthcare that has undergone and will continue to undergo several transformations through time. This review provides a comprehensive overview of current reversible hormonal and non-hormonal birth control methods as well as their mechanism of action, safety, and effectiveness specifically for individuals who can become pregnant. Additionally, we discuss the latest Food and Drug Administration (FDA)-approved hormonal method containing estetrol and drospirenone that has not yet been used worldwide as well as the first FDA-approved hormonal over-the-counter progestin-only pills. We also review available data on novel hormonal delivery through microchip, microneedle, and the latest FDA-approved non-hormonal methods such as vaginal pH regulators. Finally, this review will assist in advancing female contraceptive method development by underlining constructive directions for future pursuits. Information was gathered from the NCBI and Google Scholars databases using English and included publications from 1900 to present. Search terms included contraceptive names as well as efficacy, safety, and mechanism of action. In summary, we suggest that investigators consider the side effects and acceptability together with the efficacy of contraceptive candidate towards their development.

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“…Formulated into a vaginal film (ZB-06), HCA was recently tested in women in a phase I clinical trial. Not only was the antibody film safe, it effectively eliminated progressively motile sperm in cervical mucus in the post-coital test ( 45 ). Multivalent variants of HCA, which are 10–100 times more potent than the parent HCA IgG mAb, are currently being developed for potential use as second generation mAbs in contraceptive films and intravaginal rings ( 46 ).…”

Section: Mabs As Immunocontraceptionmentioning

confidence: 99%

“…HIV mAbs have been produced at scale using plant platforms, in particular VRC01 and P2G12 ( 7 , 75 ). Antibodies used in the MB66 and ZB-06 MPT clinical trials were produced in nicotiana plants and were deemed safe and effective ( 7 , 45 ).…”

Section: Cost-effective Mab Manufacturing Platformsmentioning

confidence: 99%

Innovations in monoclonal antibody-based multipurpose prevention technology (MPT) for the prevention of sexually transmitted infections and unintended pregnancy

Dohadwala,

Geib,

Politch

et al. 2024

Front. Reprod. Health

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Monoclonal antibodies (mAbs) are currently being produced for a number of clinical applications including contraception and the prevention of sexually transmitted infections (STIs). Combinations of contraceptive and anti-STI mAbs, including antibodies against HIV-1 and HSV-2, provide a powerful and flexible approach for highly potent and specific multipurpose prevention technology (MPT) products with desirable efficacy, safety and pharmacokinetic profiles. MAbs can be administered systemically by injection, or mucosally via topical products (e.g., films, gels, rings) which can be tailored for vaginal, penile or rectal administration to address the needs of different populations. The MPT field has faced challenges with safety, efficacy, production and cost. Here, we review the state-of-the-art of mAb MPTs that tackle these challenges with innovative strategies in mAb engineering, manufacturing, and delivery that could usher in a new generation of safe, efficacious, cost-effective, and scalable mAb MPTs.

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ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study

Cited by 11 publications

References 58 publications

Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody

Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody

Reversible female contraceptives: historical, current, and future perspectives

Innovations in monoclonal antibody-based multipurpose prevention technology (MPT) for the prevention of sexually transmitted infections and unintended pregnancy

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