Mid March, this year was another milestone in the long and tenuous journey to tackle a virus that is responsible for the death of numerous children from Diarrhoea—Rotavirus.
The low-cost vaccine that resulted from international collaborative efforts spearheaded by DBT was proved to be highly efficacious in phase 3 trails. The results of the study published in the journal Lancet showed that the vaccine significantly reduced severe rotavirus diarrhoea by more than half—56 percent during the first year of life, with protection continuing into the second year of life.
Besides, Bharat Biotech, an Indian drug manufacturing company has received the license to manufacture and sell the vaccine. May 2013 witnessed the announcement of the low-cost vaccine and the recent developments helped maintain that achievement trail. The travails of all involved were well worth it—after all, it took a lot to translate results of research to benefits of people.
Let us look at how it all begun and pieced together into a unique social innovation partnership that brought together the experience and expertise of Indian and international researchers as well as the public and private sectors.
Two occurrences—a brilliant young assistant professor at the All India Institute of Medical Sciences spots an interesting viral strain. He meets an equally brilliant scientist from across the Atlantic at a conference in Kolkata. More than two decades of laborious research and India is ready to launch the cheapest Rotavirus vaccine.
A few months ago, when the vaccine was announced, it made headlines. One saw the smiling faces of the scientists, officials and the executives behind the endeavor.
Later, there were comments too that if the amount of money that was spent on ROTAVAC could be given to others, more such products could see the light of day. But, it is not just (essential) resources that make for science and application, it is principally the people. The challenge is to build more such teams.
Teams that are ready to pursue a dream till it bears fruit.
At this juncture, it is relevant to tell the world the story of the inspired pursuance of the dream, the tireless research, the commitment to the goal, the sacrifices, the heartbreaks and the long, patient wait—precisely everything that the team went through.
It was the early 1980s. Dr MK Bhan was then an assistant professor at India’s premiere medical institute, the All India Institute of Medical Sciences. He noticed a strain of rotavirus behaving in a very strange manner. It infected newborn babies but the little ones did not develop diarrhoea.
In 1985, Dr Bhan was attending a WHO meeting at Kolkata. There he met Dr. Roger Glass, a diarrhoeal expert working at Centre for Disease Control and Prevention, a laboratory of the National Institute of Health, USA, and intrigued as he was about this strain, discussed it with Dr Glass.
The venue too was an interesting one. Kolkata–where Russian scientist Waldemar Mordecai Wolff Haffkine had worked on the Cholera vaccine and Sir Ronald Ross identified the parasite responsible for malaria. Perhaps such a legacy played a role in fostering another collaboration that would also prove to be historic.
Keen to exchange knowledge, they stated an informal joint research programme. The informal relationship continued for a few years till in 1989-1990, the Department of Biotechnology, Ministry of Science & Technology, Government of India, along with NIH and UNSAID was inspired enough to provide the first funding.
“The scope of the research seemed to be a very bright one and so we decided to fund it,” recalls Dr TS Rao, Senior Advisor at the Department of Biotechnology.
Funding, of course, intensified the activity.
The original team that started work on the neonatal rotavirus infection and its effects comprising Dr MK Bhan, Dr Ramesh Kumar and Dr Nita Bhandari received a boost to increase the pace of their work.
“Dr Bimal Das from the AIIMS, who joined the group subsequently, visited CDC to characterise the strain, which turned out to be a novel assortant of the human rotavirus strain with a single VP4 gene segment replacement of bovine origin,” recalls Dr Glass.
What Dr Glass meant was that when different stains attack the same host sometimes mixing of genetic material of the stains occurs to form a new strain.
The strain now called 116E which had not been seen previously, was characterised as genotype G9P11. Dr Jayashree Ayer, Dr Bhan’s PhD student at AIIMS indicated that after the infection with this strain, the new born’s serum and mucous systems were geared up to build a firewall to any infection of rotavirus.
In parallel, Dr C Durga Rao of the Indian Institute of Science, Bangalore, with Dr Harry Greenberg from Stanford University, also started working on another similarly promising strain of rotavirus called I321.
For more than two decades, the two independent research teams worked in parallel under the auspices of the Indo-US Vaccine Action Program (VAP), a bilateral programme implemented since 1987 by DBT and NIAID/NIH, to study the two different naturally occurring, weakened strains and develop new rotavirus vaccines for infants.
NIH contracted with DynCorp to produce clinical-grade pilot lots of the vaccines in 1997 and evaluate those lots in American adults and children prior to shipping them to India. In 1998, VAP solicited commercial partners in India for the next stage of development and identified Bharat Biotech International Ltd., a Hyderabad-based vaccine manufacturing company, to develop both vaccine candidates.
In 2000, a consortium of partners including Bharat Biotech, CDC, NIH, AIIMS, Stanford University and IISc, submitted a proposal to PATH and DBT for support to move the two vaccine candidates through production, testing, and surveillance. Through the Bill & Melinda Gates Foundation-funded Children’s Vaccine Program, PATH joined the collaborative effort in 2001.
Thus was formed a unique group committed to social innovation and inspired to reach vaccine to the suffering people at an affordable price.
In 2003, Bharat Biotech convened the various partners to discuss the clinical development plan for the 116E and I321 vaccine lots. Trials conducted in 2005 showed that while both of them were safe, 116E provided significantly better protection to the disease.
Each of the partners played a very important role.
According to Nita Bhandari, a Public Health Researcher who coordinated the clinical trials and the multi-investigator, multi-agency programme, described it as a challenging task as was building trust among them and maintaining it for a long period. “We had to learn continuously and execute brilliantly, over a long period of time,” she pointed out.
The sharing of the costs of development between several partners played a crucial role in limiting the price of the vaccine to just $1 per dose.
Bharat Biotech says that highly efficient manufacturing process and innovative product development efforts also contributed to keeping the costs low.
The other mandatory trials and permissions and other procedures for drug development took about a decade more and we came out with what is a truly Indian vaccine—the strain was an Indian one, so was the company a brave young one with a dynamic CEO with a never say die attitude and, of course, the trials which involved scores of Indians.
The international collaboration in this vaccine is not to be underestimated and the best and the brightest in the vaccine field came together for this vaccine, which, hopefully, can be used the world over.
Part of this article has been reused from Professor K VijayRaghavan’s blog, where the chronicle of the development of the ROTAVAC was written last year.