Hilleman Labs is developing a liquid form of meningococcal vaccine in a single container closure

Hilleman Labs (HL) has been working on the development of vaccine technologies against some of the key causes of bacterial meningitis. Akanki Sharma speaks to Dr Manoj Kumar, Senior Director – R&D, Hilleman Laboratories to find out more details about the vaccine, the technology and science behind its development and how it would help tackle the significant disease burden posed by meningitis in India

How huge is the disease burden of meningitis in India? 

Although meningococcal disease surveillance in India is not routine and data on endemic disease are lacking, the country is known to experience occasional outbreaks. The small amount of data suggests multiple meningococcal outbreaks in the 1980s in Delhi, Gujarat, Andhra Pradesh, Madhya Pradesh, and Orissa and more recently 2000’s outbreaks have occurred in Delhi and North Eastern states. The outbreaks showed a high fatality rate and with a high prevalence of meningococcal serogroup A. On an average between 3000-4000 annual cases with around 250-300 deaths have been reported due to meningococcal meningitis in India in recent years. Due to the lack of enough meningococcal epidemiological data in India, these numbers might be underestimates of the actual meningococcal disease burden.

Share a brief about the ongoing vaccine research at Hilleman Laboratories to combat meningitis 

Meningitis is a disease of the central nervous system, more specifically inflammation of meninges, the coverings of the brain and spinal cord, which can affect people of any age group. There are several causes of meningitis which include viral and bacterial infections. Hilleman Labs (HL) has been working on the development of vaccine technologies against some of the key causes of bacterial meningitis, which include Neisseria meningitidis (Meningococcus), Haemophilus influenzae type B (Hib) and Group B streptococcus (GBS). We have completed pre-clinical studies of improved Hib conjugate vaccines and are working on the development of novel meningococcal conjugate vaccines. Besides this, we have also initiated work on the development of a GBS conjugate vaccine candidate. Our vaccine R&D portfolio covers bacterial meningitis to a great extent including causes of maternal and infant mortality. 

What is the form and dosage of the vaccine you are working on? How will it enable better outcomes than the existing vaccines for meningitis? 

Hilleman Labs is targeting the development of a liquid form of the meningococcal vaccine in a single container closure which will enable a reduction in cost and help easy administration of the vaccine as compared to most other meningococcal vaccines which are developed fully or partially based on lyophilization technology and require two container closures to be handled.

What are the challenges in developing a vaccine for meningitis? 

Meningococcal conjugate vaccine development as with any other conjugate vaccine is quite complex which involves the production of different antigens (polysaccharides) and carrier proteins by multiple fermentations or organic synthesis in the synthetic approach, followed by their purification, conjugation and vaccine formulation. At each stage, the intent is to reduce the process losses and shorten the processing time. Finally, each batch of a multi-valent vaccine requires several analytical tests to confirm the quality of the vaccine. Finally, to develop a vaccine to be stable in liquid formulation requires significant experiments and defining the formulation combinations. The optimised formulation becomes further important when a component of the vaccine is known to be prone to degradation due to its chemical structure e.g. meningococcal serogroup A polysaccharide in this case.  

What’s the cost incurred on this development? In addition, are you getting any financial aid for this vaccine? 

Hilleman Labs is developing the technologies for manufacturing readiness which takes years of scientific research. Normally, vaccine development until the establishment of proof of concept ranges from $2-20 million or even more, based on the type of innovation/technology, the span of research and development, and the type of the vaccine construct. Presently, Hilleman Labs has invested in research to develop vaccines for meningitis.

How will it prove to be a high-impact, low-cost vaccine and when is it expected to come into the market? 

Meningitis, in general, is a severe disease and could prove fatal if not treated early. Even after treatment, a significant percentage of those recovered develop some form of long-term sequelae. Hence, effective vaccines covering as many meningitis causing organisms will be of high impact. 

Some of these complex vaccines may be more expensive to make, but the development of affordable vaccines is at the core of Hilleman’s vision and mission. HL’s focus has been to reduce the cost of manufacture by exploring innovative technologies e.g. synthetic approach or by improving traditional processes e.g. by increasing yields and reducing process times. 

In general, at least four to six years are needed after the pre-clinical proof-of-concept to get a vaccine licensed. In our case, we work with a manufacturing partner to take the vaccine to licensure and to make it available for use. This would add some additional time to vaccine licensure and availability in the market.      

Tell us about the vaccines currently available for meningitis around the world? 

There are multiple licensed vaccines available for Hib and meningococcal infections. Currently, available meningococcal vaccines are quite costly and unaffordable for common use in developing countries. Similarly, Hib adds the highest portion to the cost of Hib containing multivalent vaccines. Hence, we at Hilleman Labs are working on developing affordable technologies.

Does your vaccine utilise synthetic conjugate vaccine technology? Please elaborate about it

The synthetic technology is a recent approach to develop and manufacture polysaccharide conjugate vaccines. This replaces the bacterial polysaccharide antigen which needs handling of pathogenic bacteria. Due to the advances in organic chemistry, the bacterial polysaccharide fragments (oligosaccharides) can be synthesised using simple chemicals without a need to grow bacteria. This helps significantly in biosafety aspects of vaccine development and reduces facility costs. The synthetic oligosaccharides mimic the bacterial polysaccharides in generating desired immunity. Further, the synthetic process is highly repeatable and easily scalable. We have worked on the development of synthetic oligosaccharides for different pathogens, and the pre-clinical development is in progress. A successful development of a synthetic approach based meningococcal vaccines would reduce the cost of this vaccine, making it affordable and increasing its, use especially among the poorer populations. This will help in further reduction of meningitis disease burden in these populations. Disease eradication is a far-reaching goal, however, global efforts are ongoing for significantly minimising meningitis burden by 2030 by mixed approaches including vaccination.

With regards to the meningitis vaccine market, what are the rising trends, demands and analyses across the world? 

As per a report published in 2019, UNICEF procured 401 million doses of meningococcal vaccines during 2010-2018 for 22 countries and they are anticipating a demand of another 68 million doses by 2021. There is a supply deficit for Meningococcal C and W containing vaccines and would require an additional supply of affordable vaccines for the emergency stockpile. 

In 2017, the revenue from the global meningococcal vaccine market was estimated to be $2.3 billion which is expected to reach $6 billion by 2028 with a compound annual growth rate of ~9.2 per cent every year over the next 10 years between 2017-2028.