NIH Clinical Center
Posted on by Dr. Francis Collins
The winter holidays are traditionally a time of gift-giving. As fatiguing as 2020 and the COVID-19 pandemic have been, science has stepped up this year to provide humankind with a pair of truly hopeful gifts: the first two COVID-19 vaccines.
Two weeks ago, the U.S. Food and Drug Administration (FDA) granted emergency use authorization (EUA) to a COVID-19 vaccine from Pfizer/BioNTech, enabling distribution to begin to certain high-risk groups just three days later. More recently, the FDA granted an EUA to a COVID-19 vaccine from the biotechnology company Moderna, Cambridge, MA. This messenger RNA (mRNA) vaccine, which is part of a new approach to vaccination, was co-developed by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The EUA is based on data showing the vaccine is safe and 94.5 percent effective at protecting people from infection with SARS-CoV-2, the coronavirus that causes COVID-19.
Those data on the Moderna vaccine come from a clinical trial of 30,000 individuals, who generously participated to help others. We can’t thank those trial participants enough for this gift. The distribution of millions of Moderna vaccine doses is expected to begin this week.
It’s hard to put into words just how remarkable these accomplishments are in the history of science. A vaccine development process that used to take many years, often decades, has been condensed to about 11 months. Just last January, researchers started out with a previously unknown virus and we now have not just one, but two, vaccines that will be administered to millions of Americans before year’s end. And the accomplishments don’t end there—several other types of COVID-19 vaccines are also on the way.
It’s important to recognize that this couldn’t have happened without the efforts of many scientists working tirelessly behind the scenes for many years prior to the pandemic. Among those who deserve tremendous credit are Kizzmekia Corbett, Barney Graham, John Mascola, and other members of the amazing team at the Dale and Betty Bumpers Vaccine Research Center at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
When word of SARS-CoV-2 emerged, Corbett, Graham, and other NIAID researchers had already been studying other coronaviruses for years, including those responsible for earlier outbreaks of respiratory disease. So, when word came that this was a new coronavirus outbreak, they were ready to take action. It helped that they had paid special attention to the spike proteins on the surface of coronaviruses, which have turned out to be the main focus the COVID-19 vaccines now under development.
The two vaccines currently authorized for administration in the United States work in a unique way. Their centerpiece is a small, non-infectious snippet of mRNA. Our cells constantly produce thousands of mRNAs, which provide the instructions needed to make proteins. When someone receives an mRNA vaccine for COVID-19, it tells the person’s own cells to make the SARS-CoV-2 spike protein. The person’s immune system then recognizes the viral spike protein as foreign and produces antibodies to eliminate it.
This vaccine-spurred encounter trains the human immune system to remember the spike protein. So, if an actual SARS-CoV-2 virus tries to infect a vaccinated person weeks or months later, his or her immune system will be ready to fend it off. To produce the most vigorous and durable immunity against the virus, people will need to get two shots of mRNA vaccine, which are spaced several weeks to a month apart, depending on the vaccine.
Some have raised concerns on social media that mRNA vaccines might alter the DNA genome of someone being vaccinated. But that’s not possible, since this mRNA doesn’t enter the nucleus of the cell where DNA is located. Instead, the vaccine mRNAs stay in the outer part of the cell (the cytoplasm). What’s more, after being transcribed into protein just one time, the mRNA quickly degrades. Others have expressed concerns about whether the vaccine could cause COVID-19. That is not a risk because there’s no whole virus involved, just the coding instructions for the non-infectious spike protein.
An important advantage of mRNA is that it’s easy for researchers to synthesize once they know the nucleic acid sequence of a target viral protein. So, the gift of mRNA vaccines is one that will surely keep on giving. This new technology can now be used to speed the development of future vaccines. After the emergence of the disease-causing SARS, MERS, and now SARS-CoV-2 viruses, it would not be surprising if there are other coronavirus health threats in our future. Corbett and her colleagues are hoping to design a universal vaccine that can battle all of them. In addition, mRNA vaccines may prove effective for fighting future pandemics caused by other infectious agents and for preventing many other conditions, such as cancer and HIV.
Though vaccines are unquestionably our best hope for getting past the COVID-19 pandemic, public surveys indicate that some people are uneasy about accepting this disease-preventing gift. Some have even indicated they will refuse to take the vaccine. Healthy skepticism is a good thing, but decisions like this ought to be based on weighing the evidence of benefit versus risk. The results of the Pfizer and Moderna trials, all released for complete public scrutiny, indicate the potential benefits are high and the risks, low. Despite the impressive speed at which the new COVID-19 vaccines were developed, they have undergone and continue to undergo a rigorous process to generate all the data needed by the FDA to determine their long-term safety and effectiveness.
Unfortunately, the gift of COVID-19 vaccines comes too late for the more than 313,000 Americans who have died from complications of COVID-19, and many others who’ve had their lives disrupted and may have to contend with long-term health consequences related to COVID-19. The vaccines did arrive in record time, but all of us wish they could somehow have arrived even sooner to avert such widespread suffering and heartbreak.
It will be many months before all Americans who are willing to get a vaccine can be immunized. We need 75-80 percent of Americans to receive vaccines in order to attain the so-called “herd immunity” needed to drive SARS-CoV-2 away and allow us all to get back to a semblance of normal life.
Meanwhile, we all have a responsibility to do everything possible to block the ongoing transmission of this dangerous virus. Each of us needs to follow the three W’s: Wear a mask, Watch your distance, Wash your hands often.
When your chance for immunization comes, please roll up your sleeve and accept the potentially life-saving gift of a COVID-19 vaccine. In fact, I just got my first shot of the Moderna vaccine today along with NIAID Director Anthony Fauci, HHS Secretary Alex Azar, and some front-line healthcare workers at the NIH Clinical Center. Accepting this gift is our best chance to put this pandemic behind us, as we look forward to a better new year.
Coronavirus (COVID-19) (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
Dale and Betty Bumpers Vaccine Research Center (National Institute of Allergy and Infectious Diseases/NIH)
Moderna (Cambridge, MA)
Pfizer (New York, NY)
BioNTech (Mainz, Germany)
Posted on by Dr. Francis Collins
On March 19, 2020, California became the first U. S. state to issue a stay-at-home order to halt the spread of SARS-CoV-2, the novel coronavirus that causes COVID-19. The order shuttered research labs around the state, and thousands of scientists began sheltering at home and shifting their daily focus to writing papers and grants, analyzing data from past experiments, and catching up on their scientific reading.
That wasn’t the case for everyone. Some considered the order as presenting a perfect opportunity to volunteer, sometimes outside of their fields of expertise, to help their state and communities respond to the pandemic.
One of those willing to pitch in is Jennifer Doudna, University of California, Berkeley (UC Berkeley) and executive director of the school’s Innovative Genomics Institute (IGI), a partnership with the University of California, San Francisco (UC San Francisco). She is also recognized as a pioneer in the development of the popular gene-editing technology called CRISPR.
Doudna, an NIH-supported structural biochemist with no experience in virology or clinical diagnostics, decided that she and her IGI colleagues could establish a pop-up testing lab at their facility. Their job: boost the SARS-CoV-2 testing capacity in her community.
It was a great idea, but a difficult one to execute. The first daunting step was acquiring Clinical Laboratory Improvement Amendments (CLIA) certification. This U. S. certification ensures that quality standards are met for laboratory testing of human blood, body fluid, and other specimens for medical purposes. CLIA certification is required not only to perform such testing in the IGI lab space, but for Doudna’s graduate students, postdocs, and volunteers to process patient samples.
Still, fate was on their side. Doudna and her team partnered with UC Berkeley’s University Health Services to extend the student health center’s existing CLIA certification to the IGI space. And because of the urgency of the pandemic, federal review of the extension request was expedited and granted in a few weeks.
The next challenge was technological. Doudna’s team had to make sure that its diagnostic system was as good or better than those of other SARS-CoV-2 testing platforms. With great care and attention to lab safety, the team began assembling two parallel workstreams: one a semi-manual method to get going right away and the other a faster, automated, robotic method to transition to when ready.
Soon, patient samples began arriving in the lab to be tested for the presence of genetic material (RNA) from SARS-CoV-2, an indication that a person is infected with the virus. The diagnostic system was also soon humming along, with Doudna’s automated workstream having the capacity to process 384 samples in parallel.
The pop-up lab—known formally as the IGI SARS-CoV-2 Diagnostic Testing Laboratory—is funded through philanthropy and staffed by more than 50 volunteers from IGI, UC Berkeley, UC San Francisco, and local data-management companies. Starting on April 6, the lab was fully operational, capable of running hundreds of tests daily with a 24-hour turnaround time for results. A positive test requires that at least two out of three SARS-CoV-2 genomic targets return a positive signal, and the method uses de-identified barcoded sample data to protect patient privacy.
Doudna intends to keep the pop-up lab open as long as her community needs it. So far, they’ve provided testing to UC Berkeley students and staff, first responders (including the entire Berkeley Fire Department), and several members of the city’s homeless population. She says that availability of samples will soon be the rate-limiting step in their sample-analysis pipeline and hopes continued partnerships with local health officials will enable them to work at full capacity to deliver thousands of test results rapidly.
Doudna says she’s been amazed by the team spirit of her lab members and other local colleagues who have come together around a crisis. They’ve gotten the job done by contributing their different skills and resources, including behind-the-scenes efforts by the university’s leadership and staff, philanthropists, city officials, and state government workers.
Although Doudna and her team intend to publish their work to help others follow suit , she says the experience has also provided her with many intangible rewards. It has highlighted the value of resilience and adaptation, as well as given her a newfound appreciation for the complexity and precision of operations in the commercial clinical labs that are a routine part of our medical care.
Although the COVID-19 pandemic seems to have thrust all of us into a time warp, in which weeks sometimes feel like months, there is much to do. The amount of work needed to tame this virus is significant and requires an all-hands-on-deck mentality, which NIH and the biomedical research community have embraced fully.
Doudna is not alone. Other labs around the country are engaged in similar efforts. At the NIH’s main campus in Bethesda, MD, staff at the clinical laboratory in the Clinical Center rapidly set up testing for SARS-CoV-2 RNA, and have now tested more than 1,000 NIH staff. Researchers at the Broad Institute of MIT and Harvard partnered with the city of Cambridge, MA, to pilot COVID-19 surveillance in homeless shelters and skilled nursing and assisted living facilities located there.
Hats off to everyone who goes the extra mile to get us through this tough time. I am so gratified when, guided by compassion and dogged determination of the human spirit, science leads the way and provides much needed hope for our future.
 Blueprint for a Pop-up SARS-CoV-2 Testing Lab. Innovative Genomics Institute SARS-CoV-2 Testing Consortium, Hockemeyer D, Fyodor U, Doudna JA. 2020. medRxiv. Preprint posted on April 12, 2020.
Coronavirus (COVID-19) (NIH)
CLIA Law & Regulations (Centers for Disease Control and Prevention)
Innovative Genomic Institute (Berkeley, CA)
Doudna Lab (University of California, Berkeley)