The R&D efforts and Project Selection at Hilleman Lab primarily focus on the following:
Hilleman Labotaries located at Jamia Hamdard University in New Delhi includes GLP (Good Laboratory Practices) compliant R&D laboratories focused on bacterial fermentation, cell culture, downstream processing and formulation. Our R&D center also taps new innovation and technologies to explore promising research concepts for improving immunization conditions in developing countries.
Hilleman Laboratories aims to be recognized as the Center of Excellence for early-stage development of vaccines by bringing together the scientific prowess of global partners and funders to benefit the world’s poorest.
1. Heat Stable Rotavirus Vaccine
The World Health Organization estimates that 600,000 children under the age of 5 die annually due to rotavirus diarrhea and another two million are hospitalized. 90% of these deaths occur in developing countries.
Hilleman Laboratories aims to leverage its research functions and establish a proof of concept for the development of an optimized rotavirus vaccine that will impact the health of millions of children in developing countries. The therapeutic focus of the project has been selected because of the tremendous global impact of rotavirus diarrhea on childhood mortality.
Most deaths occur in developing countries where access to treatment is limited. Sadly every child in the world will suffer a rotavirus infection before age five.
Proof of Concept
The Rotavirus vaccine study involves laboratory investigations that are aimed at examining formulations to improve product stability, ease-of-use, transportation, storage and affordability.
Hilleman Laboratories has begun to work on the development of a thermostable oral rotavirus vaccine to allow for greater temperature consistency and less reliance on exact storage timing and refrigeration.
The aim of the initial project is to heat stabilize the existing vaccine and bring it to vaccine vial monitor (VVM) 30 or higher levels. This will determine the feasibility of applying innovative delivery technologies to an existing oral rotavirus vaccine to make it thermostable for further opportunities.
This kind of R&D is needed to make effective vaccines available in resource-limited countries so that they can be more easily used to decrease the impact of vaccine-preventable diseases. There is tremendous synergy in bringing together the philanthropic, scientific and business prowess of these organizations and their funders to benefit so many of the world’s poorest.
2. Optimized Cholera Vaccine
Cholera is endemic in over 50 countries with estimated mortality of 100,000-120,000 deaths and a morbidity of 3.8-4.4 million annual cases attributed to this disease. There is an urgent need of highly effective and affordable Cholera vaccines both for outbreaks as well as mass vaccination campaigns.
Proof of Concept
The huge Cholera burden has led to a demand for an effective, low-cost Cholera vaccine for use in epidemic outbreaks as well as for mass vaccinations in endemic settings. A market also exists for travelers to endemic regions. Demand estimates for Cholera vaccines vary significantly across scenarios with an expected 30 million doses needed by 2016 rising to expected 200 million doses by 2025, assuming vaccination of all 1-14 year old patients in high risk populations. Global public health community has also expressed concern that current Cholera vaccine manufacturers may not be able to meet the projected increase in demand further strengthening the requirement for alternate, low-cost vaccine supply.
Hilleman Laboratories in collaboration with Gotovax AB (a University of Gothenburg spin-off biopharmaceutical company) aims to deliver a high impact Oral Cholera vaccine at a significantly more affordable price than the ones currently available in the market. Easy to administer, with cross protection against ETEC diarrhea and enhanced with a longer shelf life, this vaccine candidate will be most suited for geographies with the highest cholera burden like Africa and South Asia.
We also recently announced the signing of an MoU with ICDDR,B and Incepta Vaccine Ltd, both based in Bangladesh for further development and manufacturing of our vaccine.
3. ETEC Vaccine
The recent Global-Enterics Multi-centre Study (GEMS) has identified stable toxin expressing enterotoxigenic E. coli (ST-ETEC) among the top two most important diarrheal pathogens in children under 5 years of age. Thus an ETEC vaccine specific enough to distinguish between commensal E. coli and ETEC and at the same time sensitive enough to cover the diversity of ETEC is the most desired preventive measure in the diarrheal diseases space currently.
Proof of Concept
Our ETEC vaccine project involves generation of genetically modified vaccine strains that would highly express immunogenic antigens on their surface. These antigens have been selected using in-silico reverse vaccinology approaches. The latest epidemiological information together with publically available whole genome sequence (WGS) data on hundreds of ETEC has been analysed to assure the confidence in selected antigens.
ETEC strains of most commonly occuring serogroups have been selected as founder strains, which are being modified to express selected E.coli surface antigens and colonization factors for the best possible coverage of global ETEC diversity. We are working in partnership with the Wellcome Trust Sanger Institute, Cambridge, UK to formulate an oral inactivated vaccine formulation keeping in consideration needs of endemic countries.
4. Shigella Vaccine
Shigellosis is one of the leading causes of death and disability in children worldwide especially in low income developing countries of Africa and South Asia. Shigellosis results in bloody diarrhoea leading to rapid death, especially in small children. According to the 2015 Global Burden of Disease report, diarrheal diseases were collectively responsible for 1.3 million deaths across all age groups around the world. Of these, 500,000 deaths were in children less than 5 years of age, a majority of them in India. Shigella alone resulted in 164,000 deaths in total, mostly in Africa and South Asia & India. To date, there are no approved vaccines for prevention of Shigella.
Proof of Concept
Our Shigella vaccine work is a collaboration with National Institute of Cholera and Enteric Diseases, Kolkata (NICED) and the Indian Council of Medical Research (ICMR). This a strategic shift for Hilleman, since till now, our focus has been to optimise existing vaccines and address the gaps in low resource settings. With ETEC and Shigella vaccines, we endeavour to develop entirely new lines of treatment. Traditionally Shigella infection is treated with antibiotics and currently there is no vaccine to prevent Shigellosis. In view of the global emergence of multidrug resistant organisms, Hilleman Labs and NICED will develop vaccines against the infection and establish proof-of-concept in the clinic. Our partner, ICMR, brings a wealth of expertise in clinical research and development of vaccines. Together, we will accelerate development of our novel Shigella vaccine.
5. Low-cost Men ACYWX Conjugate Vaccine
Invasive disease resulting from Neisseria meningitidis infection results in 1.2 million annual cases and 135,000 deaths worldwide. As with Rotavirus and Cholera, the majority of the burden of disease caused by meningitis lies in the developing world. This includes approximately 25 countries in the African meningitis belt, regions in South-East Asia as well as in the Americas. Meningitis is also present in Europe, the Eastern Mediterranean region and in Saudi Arabia.
Neisseria meningitidis has 13 distinct serogroups, but the majority of invasive meningococcal infections are caused by organisms from the A, B, C, X, Y, or W-135 serogroups with infections in developing countries caused by serogroups A,C,Y,W & X.
While polyvalent conjugate vaccines targeting serogroups A, C, Y and W-135, are available, they are too expensive and therefore not widely used in developing countries. There are currently no low-cost polyvalent conjugate vaccines on the market that cover all five A,C,Y,W-135 and X serogroups.
Proof of Concept
Hilleman Labs has adopted a two-pronged strategy to develop low-cost combination vaccine for treatment of invasive meningococcal disease. On the one hand, we have used conventional methods to develop polysaccharide conjugate vaccines covering A,C,Y,W-135 and X serogroups. In addition, a novel method has been developed that makes use of synthetic organic chemistry to create short oligosaccharides. These oligosaccharides mimic the carbohydrate epitopes present in longer repeat units found in bacterial capsular polysaccharides. In addition, chemical linkers can be directly designed into the synthetic carbohydrates. Our method has the potential to significantly reduce costs and create new IP, allowing developing country manufacturers undertake more conjugate vaccine development projects. We have demonstrated technical success of our vaccines in animal models.