Hypothesis

COVID in the Crosshairs

With three trials in the works, the inoculation hunters at NYU Langone’s Vaccine Center are tirelessly toiling to protect human health

By Lisa Arbetter

Andrew Rubin volunteered to get sick, so you don’t have to. As a healthcare administrator and host of NYU’s Sirius Satellite/XM radio show HealthCare Connect, Rubin watched from the sidelines as the doctors and nurses with whom he works bravely put themselves at risk to help their COVID-19 patients. So when he learned that NYU was chosen to conduct human trials on an early-stage coronavirus (SARS-CoV-2) vaccine, he asked to be included. “This is my way of giving back and doing something, much like my colleagues in the hospital,” he says.

The trial is being overseen by NYU Langone Health’s Vaccine Center, which opened in 2018 to bring together the resources within the Grossman School of Medicine and Langone Health to develop and test vaccines. While it was established to tackle many diseases, “we, like most of the country’s clinical, translational, and basic science research apparatus have been focused on SARS-CoV-2, and probably will be for years,” says Mark Mulligan, director of the center as well as the Division of Infectious Diseases and Immunology.

The center concentrates on three areas: preclinical lab work, such as studying antibodies and developing vaccines; the clinical and translational—testing of those vaccines and interventions; and community outreach to educate the public about the safety and efficacy of vaccines. Right now, the center is conducting three vaccine trials. There’s the one that Rubin is part of, currently in the follow-up phase, which is testing the safety and efficacy of an mRNA vaccine developed by Pfizer and the German company BioNTech. It uses genetic code to tell cells to create an antigen that may induce an immune response, and recently became available to priority groups in the public. The second is the center’s NIH-funded clinical trial of the Oxford-AstraZeneca vaccine. This vaccine was made by adding the gene for the spike glycoprotein from SARS-CoV-2 to a weakened version of a common cold virus. The hope is that the body will learn to recognize and fight against the spike protein and, should the actual virus enter the body, keep it from infecting the cells. A Phase 3 trial of a third vaccine manufactured by Sanofi is set to begin soon.

With the RNA (Pfizer) and viral vector (AstroZeneca), a message is delivered to the body to produce the vaccine spike protein, and the body then produces an immune response to that protein—and that immune response protects against disease. With the Sanofi adjuvanted protein vaccine, no message is delivered. Rather, the vaccine spike protein itself is delivered in the vaccine and the body makes the immune response to that. “We don’t know yet if protection is provided by [that] approach—that’s why we will do the Sanofi study,” says Mulligan. The center also did both preclinical and clinical work on a treatment that uses monoclonal antibodies (taken from a sick person and cloned in a lab) to reduce the severity of COVID-19. A clinical trial of the Eli Lilly monoclonal antibody was shown “to reduce the progression to severe disease,” says Mulligan, and “hospitalizations were reduced by 80 percent.” The therapy received emergency use authorization from the FDA for outpatients at risk of becoming critically ill.

Of course, it’s all for nothing if people don’t get vaccinated, which is why outreach is equally important. Mulligan works tirelessly to advocate for the safety of vaccines, attending health fairs, organizing conferences, and testifying before the Senate. But it’s not just the coronavirus vaccines that need public buy-in. According to the center’s Vanessa Raabe, an assistant professor in the Departments of Medicine and Pediatrics, the rates of childhood vaccines have fallen since the pandemic started, leaving kids susceptible to preventable diseases like whooping cough and measles. A study released last May by the Centers for Disease Control and Prevention found that the number of vaccines given to children under 2 years old in Michigan fell drastically after the US declared a national emergency on March 13. “There are a lot of different factors that could be contributing to that,” says Raabe, who is studying how perceptions of the risks of COVID are changing behaviors. The results will shape the researchers’ strategies should there be another wave.

The center already saw a flare-up of a vaccine-preventable disease in 2019. That’s when New York City declared a public health emergency due to a measles outbreak in an Orthodox Jewish enclave in Williamsburg, Brooklyn. According to Raabe, they were collaborating with a nursing organization within that community to educate people about vaccine safety when the pandemic hit and put the effort on hold. “We are still learning about our communities,” she says. “We are open to working with community leaders to find ways to help.”

While COVID is on everyone’s mind, the Vaccine Center is anxious to resume some of its previous work, especially on an improved influenza vaccine. “Flu, every year, kills thousands of Americans,” says Mulligan. He envisions going from a once yearly shot to a universal flu vaccine given every decade to protect against all strains—by targeting the parts of the virus that don’t change from year to year. Though, he notes, “I think it’s at least 10 years away.”

It’s a good reminder that vaccines usually take a long time to develop. Mulligan got his start in vaccines working on HIV and, 40 years later, a vaccine still eludes us. When it comes to coronavirus, the trick is to find a vaccine quickly without cutting corners. “We’re running multiple aspects in parallel that would typically occur in a series,” he says. And any vaccine that shows a hint of promise will be put into mass production so it’s ready to distribute if and when testing shows it to be safe and effective.

Rubin is also doing his part to ease the minds of the vaccine-wary by tweeting every step of the way. He was dosed twice, and his blood will be monitored for the next two years to assess long-term protection and safety. Since the Pfizer vaccine is already in use, the center is offering unblinding to its volunteers so that placebo recipients can get the real thing. While he does not yet know what he received, Rubin is sure that he didn’t get a placebo because he developed aches and fever after both shots. “By the time I had a chance to get really anxious about it, it was over,” he says. “It’s a small price to pay, and insignificant compared to what the doctors and nurses did.”