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Is Old Vaccine Technology the Key to Hesitancy?

— Experts weigh whether Novavax's protein subunit strategy can convince some COVID vaccine holdouts

MedpageToday
The Novavax logo over a photo of the Spodoptera frugiperda moth.

Novavax's COVID-19 vaccine candidate could be the first authorized or approved in the U.S. to rely on a "tried and true" method for immunizing people against coronavirus.

This purified protein, or protein subunit, vaccine strategy is used in many other vaccines on the market today -- so does it have a role to play in easing hesitancy to COVID vaccines?

Experts in public health, infectious diseases, and vaccinology interviewed by ľֱ said that while there are some notable caveats, it's certainly possible that having the option could help, and that they'd welcome anything that would get more people rolling up their sleeves.

"At the end of the day, if someone is more comfortable with another vaccine, the goal should be to get people vaccinated," said Leana Wen, MD, an emergency physician and health policy expert at George Washington University and former health commissioner of Baltimore. "Having more options is always better. At this point when we have a surplus of vaccines, we should be offering individuals the choice as much as possible."

William Schaffner, MD, an infectious disease expert at Vanderbilt University Medical Center in Nashville, said there could be an advantage in the emotional appeal of a vaccine strategy with an apparent track record.

"Psychologists tell us that facts are essential, but what changes behavior is how people feel about something," Schaffner told ľֱ. "They have to feel comfortable and reassured. ... Anything that will persuade some people to make them feel more comfortable in accepting a vaccine is something I endorse."

But the available data on mRNA and adenoviral vector vaccines accumulated over the last 6 months shouldn't be overlooked, they noted.

Purified Protein Technology

For Novavax's protein subunit vaccine candidate (known as ), spike protein is made by infecting cultures of insect (Spodoptera frugiperda) cells with a baculovirus that's been altered to contain genes for making the spike. The cells then churn out spike proteins, which are purified and mixed with an adjuvant to make the vaccine.

The Novavax candidate contains the "Matrix-M" adjuvant, which is composed of the plant-derived glycoside saponin, cholesterol, and phospholipids.

Paul Offit, MD, director of the Vaccine Education Center at Children's Hospital of Philadelphia, said this is the exact same technology used in the Flublok influenza vaccine, and is similar to other purified protein vaccines that have been around for a long time, like the hepatitis B vaccine.

Other COVID-19 vaccines using more traditional technology are in development or in use in other countries, though it's not clear they'll become available in the U.S.

Sanofi and GlaxoSmithKline that they're starting a phase III trial for an adjuvanted recombinant protein vaccine similar to the one made by Novavax. Inactivated virus vaccines, another older strategy, include Covaxin in India and Sinopharm and CoronaVac in China.

While there's certainly a track record of safety for these vaccine strategies, Offit says he's not sure this level of complexity would factor into decision-making at this point in time.

"We've seen vaccine acceptance polling rise from 30% to 40% to 70% since December. Those are the people who are reassured by reason and logic and data," Offit told ľֱ. "Then there's the access issue, that's being addressed. The third is inertia, where some people don't have a problem with it but haven't gotten around to it yet. Then there's a fourth group of science denialists who don't believe in what they're being told, or think that the disease is gone. These people won't believe in the government or the medical establishment or pharma."

There's also the fact that if a vaccine does have a side effect, it will likely show up in the first 6 to 8 weeks of use, Offit said.

"Of all the vaccines we use, in infancy, childhood, adolescence, and adulthood, none of them have any long-term effects," Schaffner said. "No vaccine has shown side effects 2 to 5 years later. That doesn't exist because there's no biological reason for it."

Schaffner said the argument could also be made that "we know vastly more about mRNA vaccines than we do about Novavax. Novavax is new whereas we've given the mRNA vaccines to 170 million people in the U.S. alone. We may know more about the safety there than we do about Novavax."

Wen said it's still important to emphasize the good safety record of the vaccines while still taking patient preference into account.

"I have no concerns about the long-term effects of mRNA vaccines," Wen told ľֱ. "That said, there are individuals who may have these concerns, and if another vaccine is what it takes to get them vaccinated, I think we should do everything we can to dispel misinformation while increasing options."

The Real Key to Hesitancy

The real way to get at vaccine hesitancy is for clinicians to understand the concerns that patients have and take them seriously, Wen said.

"We need to speak to individuals and find out the reasons for their hesitancy, without judgment and with compassion," she said. "Yes, there are some people who are truly anti-science who are not going to be convinced to get the vaccine, but they are in the minority. There are many others who have questions and concerns that need to be answered."

Schaffner added that primary care physicians, who often have existing close relationships with their patients, have a big role to play in addressing remaining hesitancy.

"We have to respect why they feel that way and try to find out what is causing it," he said. "We never disrespect the person who is hesitant. We never dismiss them or belittle them. When they realize we will take their concerns seriously, they'll tell us what their issue is. Then we'll say, that's pretty common, I've heard that before, and their anxiety is eased."

"The credibility of the doctor trying to provide the information goes up, and the patient is ready to hear you," Schaffner said. "You have to validate their concerns. If you dismiss or belittle them, you won't get anywhere."

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    Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com.