Prevention of nodules and enhancement of antibody response to genetically engineered recombinant vaccine against Human Chorionic Gonadotropin (hCG) for contraception

Abstract

Objective: Human Chorionic Gonadotropin (hCG) plays a crucial role in embryo implantation and in maintenance of pregnancy. An immuno-contraceptive approach involves the use of a recombinant hCGβ-LTB vaccine formulated with adjuvant Mycobacterium indicus pranii (MIP), to prevent pregnancy without disturbing ovulation, hormonal profiles, and menstrual cycles in women. The present work in mice was designed to address issues encountered in clinical trials conducted with hCGβ-LTB vaccine, with focus on two primary concerns. Firstly, it aimed to determine the optimal vaccine dosage required to induce a high level of anti-hCG antibodies. Secondly, it aimed to assess the safety profile of the vaccine, specifically injection site reactions in the form of nodules, observed in some of the subjects.

Methods and Results: Studies undertaken indicate that a 2 µg dose of the protein version of the vaccine, administered in mice through the intramuscular route, can induce high anti-hCG titres. Furthermore, administering a booster dose enhances the antibody response. Our findings suggest that the concentration and frequency of administration of the adjuvant MIP can also be reduced without compromising vaccine efficacy.

Conclusion: The issue of nodule formation at the injection site can be mitigated either by administering the vaccine along with MIP intramuscularly or injecting hCG vaccine and MIP at separate intradermal sites. Thus, protein vaccine administered at a 2µg dose via the intramuscular route addresses both efficacy and safety concerns.

SHORT CONDENSATION

The Phase I/II clinical trials initiated with the recombinant hCG vaccine in women revealed inadequate antibody titres in all subjects, alongside the development of nodules at the injection sites in some participants. Studies were undertaken in mice to propose potential strategies for mitigating injection site reactions and enhancing the antibody response. It was concluded that the optimum dose of the protein version of the vaccine to get high antibody titres, is 2 µg administered intramuscularly while upholding safety standards.

Keywords:

• hCG
• contraception
• recombinant vaccine
• MIP
• nodule

Acknowledgment

The authors acknowledge M/s Bharat Biotech, Hyderabad, India for making available the GMP-grade recombinant hCG vaccines.

Ethical approval

All animal studies were approved by the Institutional Animal Ethics Committee, Institute of Liver and Biliary Sciences, New Delhi, India (IAEC/ILBS/20/07; IAEC/ILBS/23/05) and were carried out in compliance with the CPCSEA animal handling guidelines.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Non-confidential data will be made available on request.

Additional information

Funding

The Indian Council of Medical Research is acknowledged for funding the Clinical trials on the hCGβ-LTB vaccine vide Project No. 5/10/17/2009-RHN dated 30.11.2017. Priyanka Tiwari is thankful to the Council of Scientific & Industrial Research, New Delhi, Govt. of India for awarding a fellowship for her doctoral work.