The public got a chance last week to hear about the development of the Covid-19 vaccine directly from the scientist who played a key role in its development and production, clinical trials physician, immunologist and virologist Dr. Barney Graham.
Rocky Mountain Laboratory (RML) in Hamilton, part of the National Institute of Allergy and Infectious Diseases (NIAID) which is part of the National Institutes of Health (NIH), has been holding an annual lecture season for some time. The last speaker in the series was Dr. Anthony Fauci in 2019 just prior to the Covid-19 outbreak. Dr. Graham, who played a key role in the development of the vaccine, was scheduled to speak in 2020. That lecture was “overcome by events” as Dr. Marshall Bloom, Associate Director of Science Management at RML, put it, referring to the pandemic.
Graham was elected to the American Society for Clinical Investigation in 1996. In 2000, the National Institutes of Health (NIH) recruited him to create a vaccine evaluation clinic (Vaccine Research Center), while also maintaining a research laboratory to focus on vaccines for three categories of respiratory viruses. He became interested in vaccines while still in medical school and has been studying vaccines and working on their development for over 40 years.
He led the first human trials on the AIDS vaccine and during the 2015–2016 Zika virus epidemic, he and Ted Pierson, chief of the Laboratory of Viral Diseases, collaborated to create a vaccine intended to prevent the Zika virus. Moving from inception to manufacturing in just three months, they began a Phase 2 clinical trial in March 2017 to measure its effectiveness. In recognition of their efforts, they were finalists for the 2018 Promising Innovations Medal. In 2021, he received the Albany Medical Center Prize. In 2022, he was awarded the John J. Carty Award for the Advancement of Science by the National Academy of Sciences.
By 2017, working alongside Jason McLellan, a structural biologist, they discovered a way to stabilize the shape of a vaccine’s spike protein. Later, this method would be applied to the Covid-19 vaccine. During the Covid-19 pandemic, Graham’s laboratory partnered with Moderna to develop vaccine technology. He was a member of the research team that designed a spike protein to combat the virus.
His research found that some virus proteins change shape after they break into a person’s cells, leading to the design of a better vaccine against respiratory syncytial virus (RSV).
In his talk Graham briefly went over the history of vaccines, noting that the first ones, for smallpox and for rabies, were developed before anyone knew what a virus was. Since then, we have learned a lot by looking at them. And the more closely we look, the more we learn.
Graham said that it was only by being able to look at a virus and actually see the spikes that the virus uses to gain entry to cells and infect them that they were able to fashion a vaccine. The initial leap beyond the microscope in getting close-up views was the electron microscope. But this has been surpassed by more modern technologies that allow a view at the microscopic level down to 3 angstroms. [A single hair follicle has a diameter of about 1 million angstroms].
It was being able to examine things on this scale that allowed them to design the spike protein used to deliver the Covid-19 vaccine. Not only that, as an off-shoot it also opened the door to developing a monoclonal antibody treatment for people already infected with the disease. To top it off, this basic protein structure can also be used in developing vaccines for all other coronaviruses. It is the springboard for vaccine delivery throughout that family of viruses.
Graham emphasized that science moves forward for the most part on basic research. He said the research done on the F-Protein was not aimed at creating a vaccine, but it provided the information they needed to create one. He said it was only in 2008 that someone started a list of all the known viruses and information about them. It turned out as time went by that the number of different viruses kept growing but the number of virus families had plateaued. He said there are 27 known viral families.
At that point they realized that, given the limited number of families, to be prepared for future pandemics it would make sense to develop a delivery method that works for each family in order to get ahead in the game. They decided to take 30 viruses through the phase one level of testing for a vaccine and another 90 to be taken through animal trials.
Graham and his team were about to begin work on the Nepah when the Covid-19 pandemic hit. They quickly pivoted to make this coronavirus the object of the trials. Once the structure of the coronavirus was solved in 2016, things went very quickly. But even this rapid movement through the system was possible only because the wheels had already been greased, so to speak.
One of the main problems plaguing vaccine development, according to Graham, is the time it takes to produce them once they are designed and then there is the on-the-ground deployment. Graham said that the incredibly quick response they were able to make to the Covid-19 pandemic by taking the vaccine from bench to bedside in a year and a half drew some skeptics to question the process. He said, “Well, it is a one-and-a-half-year story. The vaccine was authorized for use in 11 months. But it could also be told as a three-year story because that’s the period where we planned for this pathogen prototype project. Or it could be an 8-year story because that’s how long we have been working on stabilizing proteins in the right shape to make the vaccines work better. Or it could be a 15-, or 20-, or even a 40-year story because that’s when we began this search for vaccines beginning with the HIV epidemic.”
Although no vaccine has yet been developed for HIV, according to Graham, the work done in that effort is proving useful when applied to other viruses.
“My hope for the future is a little period of enlightenment,” said Graham. “That sometimes happens after epidemics. We need to find solutions for misinformation and not have it so easy to spread. Biology is not political. We have to remove the politicization of biology if we are really going to solve biological problems. We have to find better ways of engendering trust for primary health providers, doctors, nurses and hospital employees who took care of these patients and have exhausted themselves and many died before they could get the vaccine and now, they are being vilified. Somehow as a society we have to get past this.”
He said there was also a great need for more funding for basic science. “All this came from basic science. We weren’t trying to make a vaccine in the beginning, we were just wondering how the F-Protein worked,” said Graham.
He said we need to fix the country’s degraded health care infrastructure from the 1980’s and greatly improve our ability to deploy. He’s hoping we can find ways to open doors for young people willing to learn things like microbiology and immunology. He said we need to work on policies concerning such things as who develops treatments, who decides what’s important, and who chooses. We also need to make sure that treatments are accessible and that we have the facilities to make them accessible.
“We have to work on these during peace time and between crisis,” said Graham, “because you can’t build trust during a crisis.”