[Frontiers In Bioscience, Elite, 9, 321-332, June 1, 2017]

Current status of a unique vaccine preventing pregnancy

Gursaran P. Talwar1, Kripa N. Nand1, Jagdish C. Gupta1, Atmaram H. Bandivdekar2, Radhey S. Sharma3, Nirmal K. Lohiya4

1Talwar Research Foundation, New Delhi, India, 2National Institute for Research in Reproductive Health, Mumbai, India, 3Indian Council of Medical Research, New Delhi, India, 4Department of Zoology, University of Rajasthan, Jaipur, India

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The initial hCGβ-TT vaccine
3.1. Evaluation of the consequences of partial cross-reactivity with hLH
4. Carboxy terminal peptides (CTPs) of hCGβ as immunogens
5. The Hetero-Species Dimer (HSD-TT/DT) vaccine
5.1. Phase I clinical trials on HSD-TT/DT vaccine
5.2. Phase II efficacy trials
6. Reversibility and regain of fertility
6.1. Normalcy of children born to previously immunized women
7. Revival of the vaccine against hCG
8. Recombinant DNA and protein vaccines
9. Pre-clinical toxicology studies
9.1. In rodents
9.2. In Marmosets
10. Summary
11. Acknowledgements
12. References

1. ABSTRACT

The ability of a vaccine linking beta hCG to a carrier to generate antibodies against hCG, its reversibility and safety was established by Phase I clinical trials conducted in India, Finland, Sweden, Chile and Brazil. Employing a hetero-species dimer (beta hCG-αoLH) linked to tetanus toxoid further improved the immunogenicity of the vaccine. Phase II clinical trials showed that anti-hCG titres above 50 ng/ml prevented pregnancy of sexually active fertile women without derangement of ovulation and menstrual regularity. On decline of antibodies, women conceived again to give birth to normal progeny. A genetically engineered vaccine consisting of beta hCG linked to B subunit of heat labile enterotoxin of E. coli has been made. It is expressed as DNA as well as protein. Priming with DNA followed by protein version of the vaccine generates very high titres against hCG in mice. Extensive toxicology studies in 2 species of rodents, and marmosets have shown complete safety of the vaccine. The vaccine is cleared for Clinical trials by the National Review committee on Genetic Manipulation and Drugs Controller General of India.

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Abbreviations: CTP: Carboxy Terminal Peptide, DCGI (Drugs Controller General of India), DT: Diptheria Toxoid, FSH: Follicle-stimulating Hormone, GLP: Good Laboratory Practice, GMP: Good Manufacturing Practice, hCG: Human Chorionic Gonadotropin, hCGß: ß subunit of Human Chorionic Gonadotropin, hFSH: Human follicle-stimulating Hormone, hGH: Human Growth Hormone, hLH: Human luteinizing hormone, HSD: Hetero-species Dimer, hTSH: Human Thyroid-stimulating Hormone, IAEC: Institutional Animal Ethics Committee, ICCR: International Committee for Contraception Research, IUDs: Intrauterine Devices, LH: Luteinizing Hormone, LTB: Heat-Labile Enterotoxin of E. coli, MIP: Mycobacterium Indicus Pranii, Mw: Mycobacterium w, RCGM (Review Committee on Genetic Manipulation), TSH: Thyroid-stimulating Hormone, TT: Tetanus Toxoid, US FDA: United States Food and Drug Administration, WHO: World Health Organization, α oLH: α subunit of Ovine Luteinizing Hormone , ß-oLH: ß subunit of Ovine Luteinizing Hormone

Key Words: Contraception, Fertility control, Human chorionic gonadotropin, hCG, Review

Send correspondence to: Gursaran P Talwar, The Talwar research Foundation, E-8, Neb Valley, Neb Sarai, New Delhi-110068 India, Tel: 91-011-65022405, E-mail: gptalwar@gmail.com