Development of the first Oral Cholera Vaccine and its successful testing on human volunteers

Today’s CSIR-Indian Institute of Chemical Biology was germinated as Indian Institute of Medical Research in 1935 in central Calcutta. A group of highly talented biomedical scientists propelled by the Nationalistic feeling catapulted themselves in the orbit of basic understanding of tropical diseases ravaging our country in those days. The organization was unique is being the only basic biomedical research centre in the country started without any pecuniary assistance from the Empire.

In due course, the institute set about untangling various health related objectives which provided a crucial base from where the present institute has grown. Despite the financial difficulties at the early stage, the intensity of creative and fertile scientific enterprise got of a good start as evident from a number publications in the journal Nature. After a span of so many years through a cursory glance, it is not easy to window the agonies and ecstasies of those dedicated souls.



Out of infectious diseases prevalent in our country in those days, studies on the biology of cholera bacteria and vaccine development were a priority. Cholera was originally endemic to the Indian subcontinent, with the Ganges River likely serving as a source of contamination. It was largely due to pioneering efforts of Dr. Sachimohan Mukherjee, the cholera research gained momentum. Dr. Mukherjee’s early interest was on the cholera phage, the virus that can infect V. cholerae and kill the bacteria. He developed highly successful new phage typing scheme for V. cholerae. Using this technique he showed that V. cholerae strains responsible for yearly epidemics in Bengal can be categorized into several types. Cholera phage typing was accepted as one of the most reliable technique for epidemiological characterization of V. cholerae strains (Ann. Biochem. Exp. Med. 1962, 22, 9-12) This simple technique offered a useful tool to follow the route by which infections travelled to distant places of endemic foci. The institute gained international acclaim for this new discovery and World Health Organization set up a reference laboratory in this institute.

Dr. Mukherjee’s vision and deep understanding of the cholera disease biology led him to realize the advantage of an oral cholera vaccine. The possibility of developing a live oral cholera vaccine with an avirulent culture of an El Tor vibrio strain isolated from a water source in Calcutta has been studied by his group. Detailed laboratory studies on the antigenic composition, pathogenicity and immunogenic value of the apparently apathogenic El Tor strain was studied at length. In animal studies it was shown that the vaccine strain was capable of multiplication in the gastrointestinal tract of rabbits and gives rise to antibacterial as well as to antitoxic immunity. A trial was initiated to examine the safety and immunogenicity of the proposed vaccine in humans.

The trial was carried out on 25 human volunteers from members of the staff of the Institute; most of them had not had occasion to handle cholera cultures in the laboratory. Each dose of vaccine was administered on an empty stomach and no food was allowed to the volunteers within 2 hours of an administration of vaccine. There was evidence that live vibrios were present throughout the intestinal tract although no untoward effect was produced in any of the volunteers. This was reasonable proof that the proposed vaccine is safe for human use. In spite of 2 successive passages through the human intestine there was no change in the pathogenicity of the strain. Therefore, there was little likelihood of the emergence of a virulent strain after such vaccination.

After live oral cholera vaccination, the volunteers developed both humoral and copro-antibodies (antibodies in faeces) which indicates a status of immunity of the vaccinated individuals. After one course of vaccination, consisting of 2 weekly doses, the antibody titre in blood appears to last for at least 6 months. On the other hand, the local antibodies in the form of free faecal antibodies or antibodies present in the cells of the mucous membrane of the intestinal tract are likely to play a more significant role in protection against the infecting organism. Most of the volunteers showed by the tests adopted, the presence of copro-antibodies in low titre within a short time after live oral vaccination and they continued to show the presence of these copro-antibodies. The present findings indicate that the live oral cholera vaccine consisting of an avirulent El Tor culture was safe for human use and is likely to give rise to both local and systemic antibodies (Bull. Wid. Hlth. Org 1959, 40, 503-511).

The concept that live oral cholera vaccine is possible, was shown by Dr. Sachimohan Mukherjee of this institute for the first time and opened up new avenues of further research.

Arun Bandyopadhyay
Director, CSIR-IICB