Two-dose coronavirus vaccination schedules will make it harder to inoculate America

© Jenn Ackerman for the Washington Post
On the road outside the countryside of Wessington Springs, SD, where 1 in 37 people had the virus this month.

When Molly Howell talks about the two-dose regimen needed to immunize residents of North Dakota’s 210 long-term care facilities against the coronavirus, she looks like a general marshalling massive airlift without knowing how many planes she will have.

As director of the state’s immunization program, Howell is on top of mass seasonal flu vaccinations, essentially one-stop shopping. And she’s familiar with serial vaccinations, like two-step shingle injections. But for current coronavirus vaccines, which require two injections three or four weeks apart, she predicts clinicians will need to make far more than two facility visits. Will health workers be considered a high priority group and therefore scheduled for vaccination earlier than residents at risk? How should shiftworkers be received? And what about the many people entering or exiting facilities in the window between shots?

“It will definitely be an iterative process,” Howell said, as she multiplied these problems in prisons, group homes and homeless shelters, wondering how not to waste precious doses if someone does. not showing up as expected on his second shot, leaving a vial in the fridge.

“Are you using second doses for the first doses?” Howell speculated.

As the country prepares to vaccinate tens of millions of Americans against the novel coronavirus, public health officials like her face new dilemmas, driven by the urgency of the pandemic, the fact that only a small minority can be immunized against previous exposure and with the vaccine available at each site, with different intervals between injections depending on the manufacturer.

They will need to follow up with people who have received a dose to send a reminder about the need to come back a few weeks later. They fear that the first vaccine will make people sick enough that they will not want to be tested again. And they predict problems if people get their first dose at, say, Walgreens and go to CVS for their second, or, worse yet, if they cross state borders, going through a department’s registration system. from health to another.

“Two doses more than double the logistical challenges of administering vaccines,” said Jeffrey Duchin, public health official in Seattle and King County, Wash. “The moving parts should line up.”

A two- or three-dose regimen is routine for boosting immunity against many diseases, but it is unprecedented in a pandemic when the public health goal is to immunize 60 to 70 percent of the population within a few months to achieve collective immunity and stop the virus. spread.

“This is the only time we face a serious and immediate threat to the general population that requires a two-dose vaccine,” said Kelly Moore of the Immunization Action Coalition, who was program director for Tennessee in 2009 during the H1N1 pandemic and remembers her relief when she learned about everyone but young children would only need one injection.

This was possible because unlike covid-19, which is caused by the coronavirus, influenza similar to H1N1 had already circulated in humans, giving many people partial immunity. Clinical trials have shown that protection is provided by a single injection.

With Ebola, Moore said, there are single-dose and two-dose vaccines and experts have found the best way to deploy them both in and around epidemics, depending on the availability of supplies.

It is not unusual for a vaccine to require a further increase in order to elicit a more effective immune system response. The classic schedule for vaccines that target proteins such as the spike protein on the surface of this coronavirus, Moore said, is three injections – “prime, prime, stimulate” – the second and third injections to come one and six months after the first injection. Each of the first two injections triggers the immune system and is usually followed by a modest drop in antibodies. The third shot, usually at least six months after the first, can offer long-term protection by stimulating the memory cells of the immune system, which by this point have matured and are ready to respond.

It is not yet clear whether any of the new coronavirus vaccines in development will work best with a third vaccine capable of boosting long-term protection.

“Memory cells increase gradually over at least six months,” said Claire-Anne Siegrist, professor of vaccinology at the University of Geneva and head of the World Health Organization’s Collaborating Center for Vaccine Immunology. The urgency of rising infection rates and death tolls has led to the promotion of an immediate two-step solution.

“In a growing pandemic, where efficacy must be achieved as quickly as possible, administering two doses of the primary vaccine and monitoring to see if and when a booster might be needed is the most reasonable choice,” she said. .

It is also possible that fewer doses will be sufficient.

“For all we know, all of these two-dose vaccines can work in one dose,” Duchin said.

Data will be collected as populations are vaccinated, providing more information on how best to beat this particular disease.

“I think we have to learn what is needed to maintain immunity,” said Bruce Gellin, president of global immunization at the Sabin Vaccine Institute. As we learn more, he added, we need to refine strategies and policies based on the evolution of science, with potential for revaccination in the future, as is the case. cases with the annual flu shot.

“There’s a lot of data points missing,” said John Brownstein, director of innovation at Boston Children’s Hospital, who runs Vaccine Finder, a system developed by Google ten years ago to help deploy the H1N1 vaccine.

The Vaccine Finder is designed to help people find suppliers of vaccines, from influenza to shingles, near where they live. The system does not collect personal data, however, which would be necessary to send reminders to individuals about a second coronavirus vaccine, for example.

“Right now it’s a one-sided push,” said Brownstein, who described his ambitions to rebuild the infrastructure so people can receive updates and information on scheduled vaccines.

Registering individuals and electronically reminding them of their second injection is daunting, said Sacramento County Health Director Peter Beilenson, who, like Howell, is concerned about the potential ineffectiveness of the drug’s staggered vaccinations. staff and residents in long-term care facilities and other residential facilities. .

The two-step emergency schedule will change the way many health services have organized mass immunization programs in recent years. For a decade, Vanderbilt University School of Medicine developed a program to immunize students, faculty, staff, and volunteers against the flu – a unique deal that has successfully vaccinated up to 15,000 people. in one day.

Many of these efficiencies will not be possible with the two-dose regimen.

“It’s impacting staff resources” at a time when healthcare workers are already exhausted, said Thomas Talbot, Vanderbilt’s head of infectious diseases.

Coronavirus vaccines can give headaches, fever, and other unpleasant symptoms – all good signs of the body’s immune system being put to work – but Talbot fears they may prevent people from coming back for their second dose.

Moore, who has studied another painful vaccine – two-dose shingles injections – says she is encouraged by how a large majority of people who know what to expect are coming back for their second doses despite the discomfort.

“I’m very encouraged that our experience with Shingrix is ​​that motivated people will come back as long as they are properly prepared to do so,” said Moore.

And while the challenges ahead are great, Howell said she was happy to be able to reflect on it with other experts.

“It’s heartwarming that we are all in the same position,” she said. “We are all going to understand this.”