Contraceptive vaccine bounces back
At 83, biomedical scientist Gursaran Prasad Talwar has reason to be happy. The birth control vaccine he developed at the All-India Institute of Medical Sciences (AIIMS) in New Delhi more than three decades ago is finally about to see light of the day. He talks about the vaccine's fascinating but difficult journey and hopes to see it in use during his lifetime.
doi:10.1038/nindia.2010.102 Published online 29 July 2010
Q : Your vaccine made news in 1970s and 80s. It was virtually forgotten from mid-1990s. But you have recently reported the vaccine's revival1. What makes you optimistic now?
A : I believe we now have a vaccine that can overcome the earlier drawback and can be mass produced cheaply.
Q : How does your vaccine work?
A : It targets human chorionic gonadotropin (hCG), a unique hormone made by the early embryo soon after fertilization of the egg. The hormone plays a critical role in implantation of the embryo and thereby the onset of pregnancy. Our vaccine elicits antibodies that neutralize the biological activity of hCG thus preventing the establishment of pregnancy.
Q : How did you make this anti-hCG vaccine?
A : Women are normally immunologically tolerant to hCG. To make the vaccine elicit antibodies against hCG, we linked the β-subunit of hCG to tetanus toxoid (TT) 'carrier'. The conjugate βhCG-TT generated antibodies not only against hCG but also — as a bonus — against tetanus that was the cause of many maternal deaths in India in 1970s. The immunogenicity of the vaccine was further enhanced by employing a heterospecies dimer of βhCG annealed to α-subunit of ovine LH (lutenizing hormone).
Q : Was this vaccine ever tested?
A : The basic concept of the vaccine was proven in rodents and monkeys and also in limited number of tubectomized women. After that, phase-1 safety trial was done in five centres by the Indian Council of Medical Research. About 148 women of proven fertility participated in phase-II efficacy trials while I was director of the National Institute of Immunology (NII) in New Delhi. These historic trials provided hard evidence on the ability of circulating anti-hCG antibodies to prevent pregnancy without interfering with ovulation and menstrual regularity.
Q : What was the problem with this vaccine then?
A : The only shortcoming was it induced sufficient antibodies in only 60–80% of the women tested while, for fertility control, efficacy above 90% is required and desirable. Thus, immunogenicity of the vaccine had to be improved to make it practicable for fertility control. All the while we had to contend with ill-informed criticism from interested lobbies that the birth control vaccine will sterilize women forever. After I retired from NII, research and development on the hCG vaccine was put on low gear. I continued the work with some of my colleagues at the Talwar Research Foundation which I founded.
Q : What is the cause of your optimism now?
A : Research on this vaccine got revived in 2006 thanks to grant from the Department of Biotechnology under Indo-US programme. Now we have made a recombinant vaccine consisting of βhCG linked at C-terminal to B-subunit of heat labile enterotoxin of E. coli. The engineered construct has been expressed in yeast (Pichia pastoris) with good yield, rendering it amenable to industrial production at low cost. The vaccine adsorbed on alum — a permitted adjuvant for human use — has generated high antibody titres in every mouse immunized with it. Used along with Mycobacterium indicus pranii — an immunomodulator approved by the Drugs Controller General of India and USFDA for human use — it generates several fold higher titres than the protective threshold in 100% mice tested.
Q : You have reported that your vaccine can be also used for treating cancer. Can you please elaborate?
A : Of late many reports have appeared on the expression of hCG/βhCG by a variety of cancers. Thus a safe vaccine generating high amounts of antibodies against hCG may find utility in treatment of advanced stage cancers expressing hCG/βhCG.
Q : Having improved upon your original vaccine by making it many times more immunogenic, what is the next step you intend to take?
A : First we intend to get the animal toxicological data for our recombinant vaccine. The study on rodents is going to be done at the National Institute of Nutrition in Hyderabad and simultaneously on monkeys at the National Institute for Research in Reproduction in Mumbai. Then, if everything goes well, we will begin human trials.
Q : You mean trials on women?
A : No. Because ours is a dual purpose vaccine, we will first try it on cancer patients for whom all other remedies have failed. Once the safety and efficacy is demonstrated in terminal cancer cases we will test the anti-pregnancy effect of this vaccine on women.
Q : Who will make the vaccine for the trials?
A : The vaccine will be produced at the bio-fermentation facility at the Indian Institute of Technology, Delhi and purified at NII.
Q : In retrospect how do you look at your work on contraceptive vaccine?
A : Due to ups and downs I lost 16 years but I am happy God has kept me alive to see the vaccine's progress to the current stage. Hopefully I will see the product released for use during my lifetime. I must add that it was late Sheldon Segal, who with his sharp intellect and foresight rescued the βhCG -TT vaccine from closure by conducting valuable safety and reversibility trials in Finland, Sweden, Chile and Brazil under the International Committee on Contraception Research of the Population Council, New York.
- Purswani, S. et al. Possibility and potential of a vaccine against human chorionic gonadotropin for family planning. Curr. Sci. 99, 169-176 (2010)