BioNTech wants to use the momentum behind its successful COVID-19 vaccine tech to apply it to other diseases. This week it announced it has set its sights on malaria: of which there were an estimated 229 million cases of worldwide in 2019, with an estimated 409,000 deaths (WHO figures).
Children aged under five years old are the most vulnerable group affected by malaria, accounting for 67% of all malaria deaths.
However, the development of an efficacious vaccine has proved elusive. While more than 100 vaccine candidates have entered clinical trials, none had reached the 75% efficacy goal set by the WHO in its roadmap to tackle malaria until an University of Oxford candidate – still in development – reported 77% efficacy in children in a Phase 2b study published earlier this year.
Spurred on by 95% efficacy for its COVID-19 candidate, BioNTech is now focusing on creating a ‘safe and highly effective mRNA vaccine with durable protective immunity’.
Theoretically, the mRNA tech could be applied to many diseases beyond COVID-19 by identifying and replicating a distinctive part of the target protein (such as the spike protein on SARS-COV-2).
But Uğur Şahin, CEO of BioNTech, highlights that a vaccine for malaria has proved elusive for a reason – and that development of a vaccine against a disease must start at the root of the problems.
“First, we need to get a deep understanding of the challenges: and come up with strategies and ideas to overcome these challenges,” he highlighted in a press conference yesterday afternoon.
“Why is it so difficult to develop a successful a malaria vaccine? We believe the key challenge is that the malaria parasite circumvents recognition by the immune system. After the mosquito bite, the maleria pathogen migrates from skin to liver and invades liver cells. In this early phase, the pathogen has established multiple mechanisms to remain invisible to the immune system. It multiplies in the liver and leaves the liver cells after about a week. Then it invades blood cells and starts to multiply in large numbers. This is the first time the infection becomes symptomatic and the immune system intervenes. However, it is too late to stop the pathogen and disease.
“Our goal is to develop a vaccine which makes the malaria parasite visible and detectable by the immune system from the very beginning, when it is most vulnerable.”
How could this be done? BioNTech will explore a range of ideas: testing, for example, known antigens but also searching for better antigens. The company will engineer its mRNA tech to give strong and durable immune responses – ‘just as we did against the coronavirus’. And it will be about creating a vaccine with different layers of defence – from antibodies that neutralize the pathogen, to ways to detect a pathogen invasion, and eliminating cells that do get infected.
Other mRNA vaccine projects
BioNTech has undertaken antigen discovery processes to identify antigens for various vaccine candidates. Since 2019, is has worked with the Bill and Melinda Gates Foundation to develop Human Immunodeficiency Virus (HIV) and Tuberculosis programs and provide affordable access to vaccines to low- and middle-income countries.
For Tuberculosis, BioNTech plans to begin clinical trials for testing a vaccine candidate in 2022, around two years after the program was initiated.
The antigen discovery processes for Malaria and Tuberculosis are being conducted by specialized teams at BioNTech’s headquarters in Mainz.
Currently, BioNTech and its partners are developing vaccines against nine different infectious diseases, while the company continues to develop 15 oncology programs at clinical stage based on four different drug classes, including mRNA.
Learnings from COVID-19
While COVID-19 and malaria have many differences, Şahin says the company can apply many learnings from the last 18 months to its next vaccine.
For example, BioNTech started its COVID-19 program with four BNT candidates, which were only whittled down to the final successful BNT162b2 after Phase 1/2 clinical trials.
“What we learned from the COVID-19 program is that multiple mRNA vaccines can be tested in parallel to identify the candidate which works best in early clinical trials. This is one of the concepts we would like to apply, because today it is not known which targets are the most suitable ones. We will connect target discovery and antigen discovery with pre-clinical and clinical testing of multiple candidates."
Meanwhile, the success of the COVID-19 vaccine has already validated the mRNA technology, added Şahin - a different situation to January 2020.
“We have built up a huge safety database now, [at the] end of this year there will be more than 1 billion people who have received our vaccine, huge safety database, which makes our technology and mRNA more acceptable.”
Looking forward, BioNTech is working on improvements to logistics for the vaccine. The mRNA can now be stored for a limited time at 2-8 degrees Celsius, but the company is also looking at whether they could be transported at room temperature.
Cost 'completely unknown'
BioNTech places the costs of developing a novel vaccine at 'well above a billion euros'. Given the complexities of a malaria candidate, it says the cost here is 'absolutely unknown at this point in time'.
BioNTech will work on malaria and manufacturing initially from internal sources - helping it gain speed and get started as soon as possible. But has welcomed the backing from various organisations for later stage clinical trials or projects once the concepts have been proven.
Building up a sustainable manufacturing system
Africa currently imports 99% of vaccines administered in the country (Furthermore, the continent is the most affected when it comes to malaria: with 94% of global malaria cases and deaths).
Building up a sustainable supply network, therefore, is a ‘highly ambitious’ project requiring support from multiple partners.
BioNTech is exploring both the possibility to set up its own mRNA manufacturing facilities, or sites via partners.
Certain structures are already in place to try and spur vaccine manufacture on the continent. The WHO is helping establish technology transfer hubs, an initiative which will initially prioritize mRNA vaccine tech. The intention for these hubs is to enable to establishment of production process at an industrial or semi-industrial level, permitting training and provision of all necessary standard operating procedures for production and quality control.
The World Health Organization (WHO), European Commission and other organizations have been involved in the early planning phase of BioNTech’s Malaria project and have offered their support to identify and set up the necessary infrastructure. Collaboration with the African Union and the Africa CDC under the partnership for African Vaccine Manufacturing programme will ensure that the enabling factors such as regulatory alignment and policy transfer, as well as country coordination are in place to get the vaccines from factories to the citizens of the African Union.