Scientists Awarded Albany Prize
Scientists Awarded The Albany Prize, America’s Most Distinguished Prize in Medicine, for Research Leading to Covid-19 Vaccines
Three pioneering scientists, whose discoveries have led to innovative advances in medicine, including the vaccines for Covid-19, were presented with the 2021 Albany Medical Center Prize in Medicine and Biomedical Research, celebrating its 20th anniversary, today during a ceremony in Albany, New York. The recipients are:
- Barney S. Graham, M.D., Ph.D., former Deputy Director, Vaccine Research Center, and Chief, Viral Pathogenesis Laboratory at the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Dr. Graham retired on Aug. 31, 2021)
- Katalin Karikó, Ph.D., Senior Vice President, RNA Protein Replacement Therapies BioNTech SE, and Adjunct Professor of Neurosurgery, the Perelman School of Medicine, University of Pennsylvania
- Drew Weissman, M.D., Ph.D., the Roberts Family Professor of Vaccine Research, the Perelman School of Medicine, University of Pennsylvania
Dr. Graham’s research investigated optimal immunogen structure to induce potent neutralizing responses. Dr. Karikó and Dr. Weissman’s research focuses on the modification of nucleic acids to develop RNA therapeutics and vaccines. As one of the breakthroughs in mRNA research their findings allowed for the rapid development of mRNA-based vaccines to address the Covid-19 pandemic.
RNA (ribonucleic acid) is a vital molecule found in human cells. Pieces of RNA are used to construct proteins inside the body so that new cells can grow. There are several different types of RNA, including mRNA (messenger RNA), that is read by ribosomes, small protein-creating factories located inside of a human cell, to build proteins necessary for human life. mRNA is used in Covid-19 vaccines produced by Pfizer/BioNTech and Moderna. The U.S. Food and Drug Administration approved the Pfizer/BioNTech coronavirus vaccine for use in people 16 and over on August 23, 2021.
At a time when the importance of scientific achievement resounds around the world with more urgency than ever, The Albany Prize continues its long tradition of honoring the most profound and transformative discoveries in medicine and of celebrating important scientific researchers.
Since The Albany Prize’s inception in 2001, the annual award of $500,000 has been granted to those who have altered and positively impacted the course of medical research. In 2020, the program paused due to the pandemic, and this year the recipients of the prize will collectively receive $1 million, double its typical amount. The Albany Prize is one of the most significant prizes in medicine and science in the United States.
“I am honored and humbled to present The Albany Prize to these exceptional scientists,” said Vincent P. Verdile, M.D., the Lynne and Mark Groban, M.D. ’67, Distinguished Dean of Albany Medical College and Chair of The Albany Prize National Selection Committee. “Collectively, The Albany Prize recipients have made major contributions to science over decades as researchers, mentors, and educators. Their years of work, scientific expertise, and sheer determination played a critical role in accelerating the development of two mRNA Covid-19 vaccines. And their dedication exemplifies The Albany Prize legacy to honor scientists whose work has demonstrated significant outcomes for the betterment of humankind.”
Getting Ahead of a Pandemic
Barney S. Graham, M.D., Ph.D., an immunologist, virologist, and clinical research physician, is a pioneer in structure-based vaccine design and a thought leader on pandemic preparedness. When the genetic sequence of SARS-CoV-2 was first announced, Dr. Graham’s lab, armed with years of mRNA clinical work and safety data, solved the mystery of Covid-19 with astonishing speed. Because of this success, it is expected that mRNA technology will play a vital role in the future of vaccine development.
When he began researching a concerning childhood infection, respiratory syncytial virus (RSV), nearly four decades ago, Dr. Graham, then at Vanderbilt University, had no idea that his work might someday be crucial to deliverance from a global pandemic.
Yet, two coronavirus vaccines are founded on a design developed by Dr. Graham and his colleagues.
The mRNA vaccines developed by Pfizer/BioNTech and Moderna use the discoveries by Dr. Graham and his colleagues and fellow Albany Prize recipients Katalin Karikó, Ph.D. and Drew Weissman, M.D., Ph.D., both at the University of Pennsylvania.
The idea of creating a vaccine with messenger RNA, or mRNA, the substance that converts DNA into proteins, goes back decades. However, early efforts to create mRNA vaccines failed because the raw RNA was destroyed before generating the desired response.
Drs. Karikó and Weissman came up with the notion that modifying an element of mRNA would enable it to slip past the immune system undetected. Along with important contributions of other scientists, the modifications Dr. Karikó and Dr. Weissman discovered allowed mRNA to become a promising delivery system for both vaccines and drugs.
Another key contribution to the mRNA vaccines is the bioengineered protein developed by Dr. Graham and his collaborators. The protein design was based on the observation that so-called fusion proteins, the pieces of the virus that enable it to invade a cell, are shape-shifters, presenting different surfaces to the immune system after the virus fuses with and infects cells. Dr. Graham and his colleagues learned that antibodies against the post-fusion protein are far less effective at stopping an infection.
Dr. Graham’s lab at the National Institutes of Health (NIH) started working with Moderna in 2017 to design a rapid manufacturing system for vaccines. In January 2019, they were preparing a demonstration project, a clinical trial to test whether Dr. Graham’s protein design and Moderna’s mRNA platform could be used to create a vaccine against Nipah, a deadly virus spread by bats in Asia.
Their plans changed rapidly when they learned on January 7, 2020, that a coronavirus was causing the epidemic of respiratory disease in China.
“We agreed immediately that the demonstration project would focus on this new virus instead of Nipah,” Dr. Graham said. Moderna produced a vaccine within six weeks. The first patient was vaccinated in an NIH-led clinical study on March 16, 2020. The early results from Moderna’s 30,000-volunteer, late-stage trial showed it was nearly 95 percent effective at preventing Covid-19.
Dr. Graham is confident that carefully designed vaccines using nucleic acids reflect the future of new vaccines. “Already, two major drug companies are doing advanced clinical trials for RSV vaccines based on the designs we discovered,” he said.
In a larger sense, the pandemic may become the event that paves the way for better, possibly less expensive, and more plentiful vaccines.
“Basic research informs everything we do, and planning and preparedness can make such a difference in how we get ahead of these epidemics,” Dr. Graham said.
During his career, Dr. Graham’s primary interests were viral pathogenesis, immunity, and vaccine development. Despite his retirement, his laboratory will remain focused on respiratory viral pathogens, pandemic preparedness, and emerging viral diseases. He applied structural biology, protein engineering, and other new technologies to create vaccines for unmet needs and emerging threats, advancing the principles of precision vaccinology. He was involved in the clinical evaluation of candidate vaccines for more than 30 years and has an ongoing interest in science education and expanding research opportunities for underrepresented minorities. He has led the development and testing of new vaccines for many global pathogens, including RSV, influenza, HIV, Ebola, West Nile, chikungunya, Zika, SARS, and MERS.
“It is a great honor to be associated with Dr. Karikó and Dr. Weissman and a privilege to be among previous Albany Prize recipients,” said Dr. Graham. “I am very grateful to all those who have helped me on my journey and to my early mentors for their generosity and inspiration.”
Pioneering Messenger RNA Research
When she was in graduate school in the 1970s, Katalin Karikó, Ph.D., learned about something that would become a career-defining obsession: Messenger RNA (mRNA).
Dr. Karikó, a biochemist, believed in its enormous potential, but for decades she relentlessly explored how the single-stranded molecules of genetic code could be used to treat conditions from strokes and cancer to influenza.
In mRNA vaccine technology, synthetic mRNA is placed as a “messenger” in cells to oversee the appropriate protein production in the human body. It teaches the immune system to protect against new “invaders.” The idea is not new, but researchers could not use the mRNA without serious side effects.
Researchers began to give up on the technology, but Dr. Karikó kept insisting that it could work, enduring a fair share of rejection in the scientific community.
Drs. Karikó and Weissman investigated RNA-mediated immune activation, and in groundbreaking research, they discovered that nucleoside modifications suppress the immunogenicity of RNA. With the support of NIH, their team demonstrated the feasibility of using nucleoside-modified mRNA for protein replacement, thus opening a new field of therapy.
The breakthrough came when Dr. Karikó and her fellow Albany Prize recipient Drew Weissman, M.D., Ph.D., an immunologist, made a critical discovery at the University of Pennsylvania. To slip synthetic mRNA past the cell’s defenses, they realized that they had to tweak one of its molecular building blocks, the nucleosides that comprise a strand of RNA. Their novel solution has been described as the “biological equivalent of swapping out a tire;” essentially, the side effects could be eliminated, opening doors to develop various new vaccines and drugs. The results were published in 2005, and patents were secured.
The founding scientists of BioNTech, established in 2008 in Mainz, Germany, understood the tremendous potential of the Karikó-Weissman discovery and hired Dr. Karikó in 2013 to oversee its mRNA research.
Using the new technology, BioNTech and Pfizer together developed a coronavirus vaccine. Moderna’s vaccine is also based on nucleoside-modified mRNA.
“I’m hopeful,” Dr. Karikó said, “now that there is so much interest and excitement for research, that it will be possible to develop mRNA technology for prevention and treatment of other diseases, too.”
No Rest Until the World Has Access to the Vaccine
An international leader in RNA biology, Drew Weissman, M.D., Ph.D., Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, has a sharp focus on providing global vaccine access.
Research by Dr. Weissman and fellow Albany Prize recipient Katalin Karikó, Ph.D., laid one part of the groundwork for the mRNA vaccines for Covid-19 developed by Pfizer/BioNTech and Moderna, enabling the creation and emergency use authorization of these vaccines within nine months. Thus far, more than 370 million doses of one of these mRNA-based Covid vaccines have been administered in the United States.
“Covid-19 will continue to be a problem until at least two-thirds of the global population is vaccinated,” Dr. Weissman said, calling for efforts to minimize the inequity that has left large parts of the world without access to doses.
“There are two things that have to happen for us to get the pandemic under control and stop the variants from appearing. We have to vaccinate the entire world, and countries need to have a high enough percentage of people vaccinated – somewhere between 75-85 percent in order to reach herd immunity. Until that happens, variants will keep appearing,” he said.
Dr. Weissman’s lab is working on multiple projects to help make vaccines more accessible. “My lab and I personally have a big issue with equality of vaccine access. We are working with the government of Thailand to build its own vaccine. The country isn’t content to wait in line to buy vaccines from another country. They will soon be able to make a Covid-19 vaccine in Thailand and supply it to several surrounding low- and middle-income countries. I am also working with World Health Organization to provide similar access in Africa,” he said.
Currently, Dr. Weissman’s research focuses on RNA and innate immune system biology and applying these findings to vaccine research, therapeutics, and gene therapy. His lab is developing many vaccines for pathogens, including malaria, norovirus, influenza, C. difficile, HSV2, HIV, HCV, and vaccines for potential future pandemics, universal influenza, and pancoronavirus. His lab also develops mRNA delivery of proteins, including genetically deficient, therapeutic, and monoclonal antibodies.
Dr. Weissman’s lab has recently developed new technologies to deliver mRNA-LNPs to specific cell types with a simple injection. The cells and organs targeted thus far include lung, heart, brain, CD4+ cells, T cells, and bone marrow stem cells. New therapies are being developed to treat genetic and other disorders for diseases, such as sickle cell anemia.