In her 31 years at Stony Brook University Hospital, Dr. Sharon Nachman, has been the principal investigator of more than 30 clinical trials – at least a third of them international research studies – seeking out new vaccines as well as treatments for Lyme disease and AIDS. So it’s not surprising that she’s the hospital’s director of the Office of Clinical Trials.
But even with all her experience, she said she’s never been as busy as during the COVID-19 pandemic, especially since Stony Brook has a part in the future of a vaccine that might help to control it.
Nachman is a member of the Maternal Child HIV Network – she’s a pediatrician with an international reputation in infectious diseases in children – and her voice was firm as she explained how research networks once focused on HIV and AIDS trials have joined forces to look at COVID-19. The result was a new consortium of researchers called the COVID-19 Prevention Network, which formed under the auspices of the infectious diseases arm of the National Institutes of Health in mid-2020 to address the need for vaccines and monoclonal antibodies. Monoclonal antibodies are laboratory-made proteins capable of fighting off harmful pathogens like COVID-19 and offer a possible treatment for those infected with the virus.
“I was involved in listening and hearing all the discussions of the CoVPN,” she explained, using the acronym for the network. “And I submitted an application for our site to be one of the sites for vaccine trials. As those were rolling along, we were picked for the Novavax study.”
The Maryland-based biotechnology company, Novavax, is one of several firms working to develop vaccines to counter COVID-19 as the pandemic enters its second year. Unlike Moderna and Pfizer-BioNTech, Novavax has never brought a vaccine to market despite focusing on experimental vaccine development since its founding in 1987.
But the Coalition for Epidemic Preparedness Innovations – a global foundation based in Norway that is dedicated to the development of new vaccines – saw something in the company and invested $388 million in its vaccine. With new vigor, Novavax pushed to get the attention of the United States, finding success in the form of $1.6 billion from Operation Warp Speed, a Trump-era partnership between the Departments of Defense and Health and Human Services to fast track vaccine development.
Nachman wasn’t the only Stony Brook applicant to vie for a spot in the trial. Dr. Benjamin Luft, director and principal investigator for the Stony Brook World Trade Center Wellness program, also raised his hand. “He had a unique population that had co-morbidities and I was looking at the population of Suffolk County,” she explained. “So the CoVPN decided to merge our two applications into one application under Dr. Luft’s leadership so that we could do the Novavax clinical trial.”
The trial enrolled about 500 patients in five weeks before closing last February and contributing to the pool of 31,000 participants from across the country.
“No steps were jumped or skipped or stepped over or missed,” Nachman said. “But because of the pandemic, many people came forward to enroll in the study rather quickly. And that’s what allowed the study to complete enrollment and move on to the next step.”
Since then, Nachman has been trying, in her own words, to “juggle” the non-Novavax and non-COVID studies that are pending. One, a Lyme disease vaccine for children, was slated to take place during the summer and fall while others have been put on hold. This isn’t because of a lack of funding but rather because the side effects of these vaccines resemble the symptoms of COVID-19. “The study looking at the RSV, the Respiratory Syncytial Virus, vaccine – the side effects of that vaccine are fever and runny nose. The last thing we need during COVID is to give you a vaccine that gives you fever and a runny nose.”
And of course, there are trials that for one reason or other, didn’t get off the ground. A trial earlier in the pandemic attempted to spearhead a treatment involving estrogen patches that might reduce the severity of COVID-19 symptoms. Nachman was to be the principal investigator but the project failed to enroll enough participants.
“I think patients that came into the hospital were sick and did not want to hear about a study. There was a lot of concern in patients that we were giving them estrogen, particularly on the male side.” The reaction, she said, was, “‘I didn’t want to grow breasts’ – even when you explained to them that’s not going to happen.”
As for the two-dose, protein-based Novavax vaccine, it has been shown to be 90.4 percent effective in preventing symptomatic COVD-19 based on results from its Phase 3 clinical trials. But the company has struggled to meet its production forecasts, forcing it to delay seeking the emergency use authorization from the Food and Drug Administration that would make it the fourth vaccine available in the United States.
From the beginning, there was concern that the Novavax vaccine may not be effective in an important segment of the population – children. To find out, clinical trials are looking at adolescents and teens aged 12 to 17 years old.
Other vaccines are further along. The Pfizer vaccine has full FDA approval for anyone over 16 and emergency authorization for those between the ages of 12 and 15. Clinical trials are underway in children 5 to 11 years old. Moderna and Johnson & Johnson vaccines still only have emergency authorization for people who are at least 18 years old, but Moderna has expanded its trials in children under 12. Separate clinical trials must be conducted for children due to their disparate immune systems and responses.
This is prime territory for Nachman, who is also chief of Stony Brook Medicine’s Division of Pediatric Infectious Diseases and a professor of pediatrics. She has been pushing since last year to include children in vaccine trials.
From her office on the fifth floor of the hospital, where medical textbooks and files are organized on shelves behind her, Sharon Nachman speaks her mind. “Kids should have been studied up front when the adult vaccines were rolling out, then that would have resulted in no delay in getting kids vaccinated,” she said. “And we wouldn’t be in the position that we’re in now, where we’re not going to have an answer for kids for six to eight or maybe even longer months.”
Nachman said the practice of considering children and pregnant women as unique groups outside the mainstream has caused this situation. “As a pediatric infectious doctor, for me those are the ordinary people who need to get the vaccine,” she said. “There’s nothing special about [children] that would require you to put off studying them for months on end – and all it did was hurt the population.”
It used to be even worse, she said, pointing out that as recently as the 1990s, licenses for vaccines and other drugs were routinely granted without certain groups, such as children, being studied at all. Nachman has been advocating for decades that children and pregnant women should be included in clinical trials such as the ongoing Novavax study. “Pediatric infectious disease requires you to be passionate about what you’re doing.” she said.
“Kids should have been studied up front when the adult vaccines were rolling out, then that would have resulted in no delay in getting kids vaccinated. And we wouldn’t be in the position that we’re in now, where we’re not going to have an answer for kids for six to eight or maybe even longer months.”– Dr. Sharon Nachman
Studying these groups and getting vaccines to them are important because the coronavirus is mutating. Variants continue to show up around the world even as the highly transmissible Delta variant has become the dominant strain in the United States and other countries. “By not getting vaccinated,” Nachman said, “you encourage more variants to go around the community.”
These variants are uppermost in Dr. Kenneth Kaushansky’s thoughts. He stepped down as dean of the Renaissance School of Medicine in January but stayed on until the end of the academic year as senior vice president of Health Sciences, overseeing the hospital, the faculty practice and the health science schools. He had originally planned to step down last year after a decade on the job, but stayed on in light of the pandemic. “As ten years began to approach, here comes COVID,” he said of the convergence of his anniversary in the job and the pandemic. “It wouldn’t have looked good for me to say, ‘Hey here comes COVID, I’m out of here!’”
He was recently elected to the board of directors of the New York Genome Center, which will allow him to explore some of the big questions about COVID-19 that revolve around the variants.
“Number one – Are they more contagious? Number two – Are they more pathogenic, do they cause more severe disease all other things being equal? And number three, are they going to turn resistant to the vaccine, perhaps the most important question of all.”
He likened the process of developing vaccines against these variants as being akin to neighborhoods. “So if you look at a map of the spike protein, there are actually four different regions that almost everybody develops antibodies to … like four different zip codes.” The spike protein is what allows the virus to gain access to the cells of the respiratory tract.
He explained that someone with antibodies to at least one of these neighborhoods would have a method of neutralizing the virus. “The virus needs to really come up with four different mutations to become immune to all these different antibodies. And that’s a tough nut to crack for a virus. … No one has seen a variant with these four mutations.”
Nachman and Kaushansky agreed that the most important thing, besides the standard advice of wearing masks, is for people to get vaccinated. Now.
To the people out there who are hesitant to get vaccinated, Kaushansky offers this: “We haven’t seen people’s arms falling off. … When there is one of these extremely rare side effects, it almost always, if not always, appears within six weeks of the vaccination. We’re now at a point where 30 million people are six weeks out from their vaccination and nobody’s getting these massive long-term complications.”
As a front-line warrior against infectious diseases, Nachman described the COVID-19 pandemic as being very different from previous outbreaks she’s experienced. In 2009, the swine flu pandemic saw more than 700 million cases of the H1N1 influenza virus worldwide with an estimated death toll of 284,000, according to the Centers for Disease Control and Prevention. “There were a lot of sick patients, both adult and pediatric,” she said. “But they weren’t the same degree of sick as COVID patients.”
With more than 200 million people infected and a global death toll that has surpassed four million, COVID-19 already has a place in the history books.