## Sunday, May 10, 2015

### MenAfriVac: A novel strategy for building a vaccine

by Swapnika Ramu.

A meningitis vaccine manufactured in India has been approved for routine immunisation in Africa: a development that is being hailed as a breakthrough in global health. Equally important is the fact that the vaccine - dubbed MenAfriVac - was developed using a new approach specifically targeted towards solving public health issues in developing countries, issues that many big pharmaceutical firms choose not to get involved in for a perceived lack of market potential.

### The success of the MenAfriVac vaccine

For over a century, recurring epidemics of meningococcal A meningitis have become a significant public health problem in sub-Saharan Africa; in fact, a swathe of the continent stretching west from Senegal all the way to Ethiopia has been dubbed the meningitis belt. Meningococcal A meningitis is caused largely by the bacterium Neisseria meningitidis and can cause brain damage, hearing loss and death. Despite early detection and treatment, an estimated 5-10% of all patients die within the first 2 days after symptoms emerge. The meningitis epidemic of 1996-97 proved to be the largest in history, with 250,000 diagnosed cases and over 25,000 deaths, underscoring the urgent need for newer and more effective treatment options.

In response, representatives from some of the affected African countries partnered with the World Health Organisation (WHO) to prioritize the development of a new meningococcal vaccine. The precursor to the creation of the MenAfriVac vaccine was the Meningitis Vaccine Project (MVP), a joint effort of the WHO and the Program for Appropriate Technology in Health (PATH, a nonprofit). The MVP was funded through the Bill and Melinda Gates Foundation, and its mandate was to oversee the development and production of a safe, cost-effective meningococcal vaccine. A major player in these efforts was Pune-based Serum Institute of India Limited (SIIL), which joined
the consortium in 2004 and went on to actually produce the vaccine. While SSIL is not a listed company, it's in the CMIE database and in 2014-15 it had revenues of Rs. 36 billion.

MenAfriVac turned out to be a great success on multiple fronts. First, its production took only six years, a record time, according to the WHO. It was the first vaccine developed specifically for use in Africa, cost less than 50 cents per injection (less than 1/10th the cost of a typical new vaccine), and proved to be remarkably effective: a trial conducted in Chad showed that districts in which people had been vaccinated had 94% fewer cases of meningitis in 2012 as compared to unvaccinated districts. The vaccine also outperformed other, more expensive options from big pharma companies; in a 2011 trial, 96% of infants and toddlers immunised with MenAfriVac had antibodies in their blood, compared to only 64% of a group given a vaccine developed by GlaxoSmithKline.

By 2013, over 100 million people in the meningitis belt had been vaccinated, and the number of cases was the lowest recorded during the epidemic season over the last ten years. At present, more than 210 million people have been vaccinated, and the vaccine has now been approved for routine vaccination of infants under one year of age. Simply protecting adults against a specific disease is not enough
to eliminate epidemics, since unprotected infants are still vulnerable; a vaccine like MenAfriVac that is effective both in infants and adults will create long-term, wide-spread protection against meningitis.

Another remarkable feature of the vaccine is that it remains effective even when stored outside the cold chain, retaining its potency for up to four days when stored at temperatures up to 40 degrees Celsius. Most other widely-used vaccines, those against polio and smallpox for example, need constant refrigeration. By eliminating this requirement, the immunisation campaign can cut costs to the tune of over 12 million dollars and can target those remote areas where electricity supplies are unreliable or absent. As a result, MenAfriVac is now the first vaccine to receive WHO approval for use at ambient temperatures in developing countries.

### New models in the healthcare sector

The MVP, an alliance that started between a public health organisation (the WHO) and a non-profit (PATH) and grew to include several other international partners, states that its approach was based on a "novel strategy of facilitating and coordinating numerous partnerships across the world", which could facilitate the introduction of other orphan vaccines, whose primary markets are low-income countries in the developing world. SIIL and the Dutch company Synco BioPartners supplied the raw materials necessary for making the vaccine. The conjugation technology required to put the raw materials together to generate a functional vaccine was developed through a collaboration with the US FDA's Center for Biologics Evaluation and Research. SIIL was tasked with identifying a low-cost process for vaccine production. In effect, the MVP broke the entire vaccine development process into several pieces, each of which was the responsibility of a different partner. According to Dr. Suresh Jadhav, SIIL's executive director, this modular approach was seen as controversial, with many people "sceptical...That technologies (could come from different) places and manufacturing happen at another place; this was something unheard of."

How did the MVP achieve success with its unconventional operational model?

I spoke with Dr. Marc LaForce, founding director at the MVP, and he listed some key factors. The first was that much of the basic science around developing an effective vaccine was already in place. As he said, "You need to have pretty good science in place already for the product you want to develop. This model will not work for an AIDS vaccine, for example, where an enormous amount of basic research still needs to be done." Second, the MVP was able to exploit the gap generated by big pharma's lack of interest; they focused on a problem that was restricted to developing countries, where the economics had not driven solutions at scale. Under these conditions, the MenAfriVac model worked quite well, and in fact, a similar approach was used to generate the first conjugate typhoid vaccine.

Third, the MVP focussed on developing low-cost solutions and partnered with SIIL to leverage their considerable experience in this field. SIIL also has a long history of working with global manufacturing standards, such as those laid down by the FDA, an especially important attribute in a project with multiple players. Each partner was picked based on a global analysis and very high levels of due diligence, anticipating the level of public scrutiny that grew over time as the project marched ahead.

Dr. LaForce pointed out that the biggest challenge faced by the MVP was solving intellectual property issues around the conjugation process in vaccine development. He said, "Africans really wanted this particular product, so convincing them to introduce the vaccine wasn’t really a problem. Solving the IP issues was probably the hardest part. A lot of the conjugation and structural chemistry was already known. What we had to do was to identify chemical methods to tie two compounds together that were not already covered by patents. This was a big deal and took us quite some time to solve."

The operational model that birthed MenAfriVac holds valuable lessons for building clever, low-cost healthcare solutions in resource-poor countries while bypassing the limitations of the traditional big pharma business model. One limitation is that much of the basic science needed to develop a specific vaccine must already be available. However, given that vaccine-related research and development in India holds a good deal of potential, it is reasonable to hope that lessons from MenAfriVac can be applied towards solving some of India's most pressing healthcare problems, such as malaria and tuberculosis - diseases where the traditional big pharma approach has not yielded notable results, and that are ripe for intervention through unconventional R&D models.

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