The newest tool being used to fight COVID-19 has Dal roots.
Dr. Mathai Mammen (BSc ’89) is the global head of research and development at the Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson. Dr. Mammen and his global team of more than 13,000 scientists are responsible for the research and development of the single-shot Janssen COVID-19 vaccine, which was recently authorized in the United States and Canada and added to the World Health Organization’s list of safe and effective vaccines.
“My group and I feel extremely proud to have had a part in this,” says Dr. Mammen. “I’ve always wanted to have an impact on human life, and there’s no bigger single event that I can imagine than this on having impact on human life. There are many other projects, but this is a unique project.”
From Dal to drug design
Dr. Mammen was born in India and moved to Halifax at the age of three. He came to Dalhousie to pursue a Bachelor of Science in Chemistry and graduated with the University Medal in Chemistry and the Governor General’s Medal. He then went on to Harvard, earning both an MD and PhD.
While conducting research for his doctoral thesis at Harvard, Dr. Mammen was able to develop a revolutionary technology called multivalent drug design. He ended up founding a company called Theravance based on that research, which focuses on the development and commercialization of medicines to treat respiratory disease, gastrointestinal disorders, bacterial infections and central nervous system pain.
“This company has created not just one drug — from an idea on a piece of paper to marketable medicine — but five so far,” says Dr. Mammen.
After leading Research & Development at Theravance, Dr. Mammen was the senior vice president at Merck Research Laboratories, where he was responsible for research in the areas of cardiovascular, metabolic and renal diseases, oncology/immuno-oncology and immunology.
In his current role at Johnson & Johnson, Dr. Mammen’s mission is to focus the energy of the best research and development teams in the world at the intersection of profound unmet medical need and actionable breakthroughs in science and technology to make medicines of unequivocal benefit for humanity.
“I’m very mission-oriented and aim to impact the health of people,” says Dr. Mammen. “That’s what I’ve been trying to maximize throughout my career.”
Taking more time pays off
It was in mid-January of last year that Dr. Mammen’s team obtained the sequence of the SARS CoV-2 virus. Within 24 hours, they decided that they needed to do something about it.
“Within days of learning the sequence of the SARS CoV-2 virus, our team began work on a number of versions of that sequence, so that the researchers could go through a selection process to pick from those versions the best version that would cause the strongest multi-pronged immune response if it were made into a vaccine,” says Dr. Mammen.
Although this additional research and experimentation phase took a couple more months compared to other companies who have made vaccines, Dr. Mammen believes the strategy paid off.
“We were able to pick something that you were just able to give in a single shot, as opposed to multiple shots in order to create a robust and protective immune response against the virus,” says Dr. Mammen.
A more versatile shot
Another unique part of this vaccine was discovered during the human trial phase, which took place in the summer of 2020.
“We noticed that there was a very strong T-cell response — not just antibodies, but T-cells,” says Dr. Mammen. “Fast forward to March 2021, and this turns out to have been a very important aspect. This virus, when it infects humans, uses an extremely small part of its spike protein to make contact with the human cell’s ACE2 receptor — just half a dozen or so amino acids.”
“This small foot-print interaction makes it not that hard for the virus to mutate to change one or two amino acids to avoid the immune system’s antibodies,” continues Dr. Mammen. “And if that happens, the antibody responses that your vaccine induces become less effective. You need this other part of the immune response — the T-Cell response — in order to be reinforcing part of the immune response.”
This response from the vaccine meant that there was no difference in the efficacy in any part of the world, including in areas like South Africa where the dominant form of the virus was the potentially problematic B.1.351 variant.
“I believe that a very systematic approach to developing the vaccine led to an outcome to a multi-pronged immune response that’s now providing confidence to people that they can get protection irrespective of the variant. The T-Cells seem to respond equally, independent of how a couple amino acids on the tip of the virus’ spike protein might change,” says Dr. Mammen.
A tear-inducing moment
The vaccine was authorized for emergency use by the U.S. Food and Drug Administration (FDA) on February 27, 2021, authorized by Health Canada on March 5, 2021, and was added to the list of safe and effective vaccines by the World Health Organization on March 12. According to Dr. Mammen, this process was able to happen quite quickly.
“They spent a few weeks behind closed doors studying the data,” says Dr. Mammen. “We locked the data by the end of January, and by the end of February we had authorization from the FDA, and authorization from Health Canada on March 5.”
And the moment that the vaccine was approved can only be described as one full of joy and a huge sense of relief.
“The regulatory board voted 22-0 to approve the vaccine,” says Dr. Mammen. “That has never happened in my professional career. It was tear inducing.”
Now that the vaccine has been approved, Dr. Mammen will have the opportunity to step back, and focus on the many other important projects underway at Johnson & Johnson.
“From curing different kinds of cancer, treating autoimmune diseases to neuroscience, including Alzheimer's disease, and certain infectious diseases beyond COVID-19 — these are all areas of extremely high interest to my team,” says Dr. Mammen. “So, there’s decades of work ahead for my team and I to make a difference to the health of humanity.”
Staying connected to Dal
Dr. Mammen continues to be heavily involved in Dal. He has been on the Dalhousie Advisory Council since its creation in 2010, was the Carl C. Coffin Alumni lecturer in Chemistry in 2006 and was awarded an Honourary Doctorate (Doctor of Laws) in 2016.
“I can’t say enough about the Chemistry Department at Dal,” says Dr. Mammen. “The courses were amazing, and the professors were not only world-renowned and famous for the research they were doing, but they took genuine interest in making sure that the undergraduate population was not only educated but became interested in pursuing chemistry — which was the case for me. It sparked a lifelong interest.”