India is set to develop the world’s first Shigella vaccine, which is likely to hit the market by 2024. Will it prove to be the remedy against a disease, a leading cause of deaths amongchildren worldwide?
An exclusive vaccine for Shigella, the chronic diarrhoeal disease, will be developed in India by 2024. Hilleman Laboratories, a global vaccine research and development organisation, along with National Institute of Cholera and Enteric Diseases (NICED), an Indian Council of Medical Research (ICMR) organisation, has signed an MoU to develop Shigella vaccines.
A threat …
Sanitation and clean water access is still a major public health burden in developing countries like India. This in turn, makes them susceptible to Shigella infection, a water-borne disease. It has been one of the leading causes of death and casualties among the children aged under five with bloody diarrhoea worldwide, especially in low-income developing countries of Africa and South Asia.
“Shigella causes dysentery as well as diarrhoea that may not necessarily be associated with blood. People thought that Shigella was no longer important as we have improved the environment sufficiently. So, we would not need a vaccine for this bacterial pathogen. But very recently, there has been studies around the world demonstrating that after rotavirus, in developing countries of Asia and Africa, Shigella is the second most important pathogen. Having a vaccine will significantly impact the children who live in poorest environments,” said Prof Gagandeep Kang, Director, Hilleman Laboratories.
According to the 2015 Global Burden of Disease report, diarrhoeal diseases were collectively responsible for 1.3 million deaths across all age groups around the world. Of these, 500,000 deaths were among children less than five years of age, a majority of them in India.
Shigella alone resulted in 164,000 deaths in total, mostly in Africa, South Asia and India. To date, there are no approved vaccines for prevention of Shigella, only antibiotics are prescribed for this disease.
…. and a Made in India solution
Promising production of safe and effective Shigella vaccines, Davinder Gill, CEO, Hilleman Labs told Express Pharma, “We will develop the vaccine by 2024. The entire R&D will take place in India. This is a vaccine which would be presented for severe diarrhoea due to Shigella in children and adults.”
Gill further added, “We hope that oral formulation would be possible and our goal is to push this vaccine into earlier stages of clinical trials in the next 12 months. Since it is a new vaccine and there are no approved vaccines for Shigella, we have to go through step-by-step clinical testing. It will take atleast six to seven years to develop the vaccine. Moreover, we are pleased to collaborate with NICED and jointly develop Shigella vaccine for a disease whose basic pathology is not yet properly understood.”
“NICED comes with a variety of strengths in research and developing strategies for treatment, prevention and control of enteric infections. This will also be a strategic shift for Hilleman. Our focus will be to optimise existing vaccines and address the gaps in low resource settings. We will now endeavour to develop an entirely new line of treatment and will look forward to jointly abate this fatal disease which threatens the nation’s health,” Gill said.
Informing that such partnerships are boosting the Make in India initiative, Dr Soumya Swaminathan, Director General, Indian Council of Medical Research (ICMR) said, “This is a step in a new direction. India has immense potential in clinical research, drug and device manufacturing and we would like to see more of these types of partnerships. Across the country, a lot of research in government academic centres, including universities are done, but unfortunately more often they are not translated into anything which has a very huge public health impact. Shigella vaccine will be a very good example for Make in India concept as the work is set to be translated from lab upto product. We are keen that ICMR becomes more collaborative and partners with organisations in this direction and mutually expand capacities through cross – functional partnerships.”
Swaminathan mentioned that rotavirus vaccine was also developed through partnership with many different agencies and indicated that Government of India’s biotechnology department and ICMR both played an important role. She said that such endeavours will surely help bring in more vaccines for different other pathogens.
Different Phases of the vaccines developed
Phase 1
Safety in healthy adult volunteers absence of serious or unexpected effects, including dissemination
- Increasing dosage
- One or several dose schedule
- Open uncontrolled study
- Usually less than 50 subjects not exposed to natural disease
Phase 2
- Population is target or high risk population
- Randomized, double blind controlled study (control is reference vaccine or placebo)
- Cascade of studies to determine dose, route schedule, association with other vaccines, response in presence of pre-existing antibodies
Phase 3
- Target population-susceptible, exposed, several hundred to thosands
- Randomized, double blind, controlled trial
- Efficacy studies
- Measurement of protective effect of vaccine
- Safety profile
- Evaluation criteria are cases of disease meeting case definition
Phase 4
4Post-licensure
- Safety
- Effectiveness
- Persistence of protection
“We are committed to support through all the phases of testing as we are aware that different institutions have different strengths. For example, we have an animal testing facility of ICMR in Hyderabad. However, for phase I testing, we don’t have the facility at ICMR so it needs be carried outside. Phase II and III can be carried over in NICED, as they have done many vaccine trials,” Swaminathan added.
Talking about the efficacy of vaccine made in India, Swaminathan also said, “Any product, whether it is vaccine or any other product, has to go through a lot of phases of development. And, each phase of the product development — be it phase I (the safety studies) or phase II (immunogenicity) or phase III (efficacy study) — has to comply with all regulatory requirements. Thereafter, registration of the product is strictly followed. Each phase carries a stringent process during the development of the product.”
Innoculating against infection
Informing that vaccines are the only effective tool to fight against Shigella infection, Dr Shanta Dutta, Director, NICED said, “Shigella infection was treated with antibiotics and currently there is no vaccine to prevent it. In view of the global emergence of multi-drug resistant bugs, challenges in global drug discovery programme vaccines is the most simple, powerful and cost-effective health intervention and an effective public health tool. Our association with Hilleman Labs is in alignment with NICED’s mission to identify enteric infections, initiate appropriate multi-disciplinary research and develop strategies for treatment, control and prevention of enteric infections.”
“Candidate vaccines against the infection have been developed and tested at NICED by using the in-vitro animal models, which showed significant immune response and protection against the infection. With partnership, we are aspiring to unlock new knowledge behind enteric diseases like shigellosis and to come up with an appropriate and effective, preventive tool against this disease,” added Dutta.