With 70% of Washington residents age 16 and older having initiated their COVID-19 vaccine, the pandemic can feel, locally at least, like its grip on our lives has loosened.
But with COVID, things are never that simple.
Billions of people worldwide remain unvaccinated — including Americans who have declined the vaccine and people in other parts of the world who lack access to the shots — and as a result, more virulent and vaccine-resistant strains keep cropping up. The more infectious Delta variant is stoking worries as it sparks cases in Washington and around the U.S.
This variant and others are raising concerns about when and how immunity among the vaccinated and those who have had an infection will wane and require booster shots to keep people healthy. Now multiple Seattle-area scientists are part of clinical trials and laboratory research that’s trying to answer those questions. One uncertainty is whether the originally approved vaccines still pack enough of a punch against more dangerous variants.
“That’s exactly the kind of information we’re trying to get,” said Dr. Christine Johnston, associate professor in the Division of Allergy and Infectious Diseases at the University of Washington School of Medicine. We need to understand “when boosters might be needed and how to give them, whether we need to give the same booster as the original series [a person received], or if we can give different ones.”
On Monday Pfizer officials met with leaders at the U.S. Centers for Disease Control and Prevention to lobby for permission to give people a third dose of its vaccine. Israel, which was the first country to achieve wide-scale vaccination, has already begun administering booster shots for people with weakened immune systems. Booster shots are a standard part of the vaccination regime for many ailments.
The World Health Organization this week, however, came out with strong opposition to the moves given the inequities to access, noting that it many countries even frontline workers like doctors and vulnerable older residents are wholly unprotected.
“While many countries haven’t even started vaccinating and another country has already vaccinated the majority of its population with the two doses and is now moving to a third dose, which is the booster, it’s really not only disappointing, it’s seriously disappointing. It doesn’t even make any sense, it makes no sense,” said Dr. Tedros Adhanom Ghebreyesus, director general of the WHO, in a press conference.
Johnston likewise agrees that it’s premature to give boosters.
“We just need to develop the science and the evidence right now,” she said. “We’re going to want to have the information about whether boosters are needed and helpful. But that is definitely balancing the equity issues, and the hope that we’re going to get equitable access to vaccines, especially initial shots.”
Research on boosters
Johnston’s study will provide 15 volunteers a booster of the original Johnson & Johnson vaccine, regardless of whether they initially received that shot or the vaccines from Moderna or Pfizer.
The UW research is being funded by the National Institutes of Health and many other sites are conducting similar trials. The scientists will collect blood samples to examine participants’ immune responses at the cellular level. The study will also focus on patient safety, watching for any side effects from the boosters. The research should have some results by fall.
A second study is underway at the Center for Interventional Immunology at Virginia Mason’s Benaroya Research Institute. The Seattle center was one of the locations where the Pfizer vaccine was first tested.
That research, which is funded by Pfizer, is giving boosters of the company’s vaccine to 25 of the participants who were part of the original research cohort at Virginia Mason. The overall study will include 10,000 people at numerous locations and some volunteers will get placebo shots. Results will be analyzed every two months. Once the effectiveness of the original Pfizer doses falls below 60%, the placebo recipients will be offered the real booster.
There’s strong interest in participation. Within three hours of sending an email asking for volunteers, all of the spots were filled and there was a waiting list, said Dr. Sandra Lord, clinical director of the Center for Interventional Immunology.
But despite Pfizer’s push this week for boosters, Lord agreed with Johnston that the data isn’t yet there.
As to when a booster will be needed, “we just don’t know when that is,” Lord said. “We have to hold off on saying anything until we have clear, randomized data.”
New vaccines, or original recipes
In addition to questions about booster timing, there are uncertainties about how effective the original vaccines will be against some of the most worrisome mutations that have emerged as the disease has spread among some 188 million people worldwide.
Variants that rise to prominence are those that are better at infecting people, better at surviving vaccines or a combination of traits that make them more dangerous than the original strain that emerged in the U.S. in early 2020.
David Veesler, an associate professor in the UW’s Department of Biochemistry, is working on COVID vaccine development and studying viral mutations. His lab recently published a paper online in the journal Science on the ways in which the Epsilon variant can dodge antibodies generated by some existing vaccines or previous infections.
Epsilon, which was originally called the California variant given where it was first detected, is “modestly” good at avoiding vaccines, Veesler said. By comparison, the Alpha variant (formerly known as the UK variant or B.1.1.7), which is currently dominant in the U.S., is more easily targeted. The Beta variant (formerly known as the South Africa variant or B.1.351) reduces the effectiveness of vaccines to a larger extent. A UK study in May reported that vaccines were slightly less effective against the Delta variant, which was first identified in India.
However, preliminary research, including work by Veesler’s lab and others, suggests that boosters of the original vaccines might still be helpful despite the vaccine resistance seen in some of the new variants. Studies on macaques that received a booster shot, as well as unvaccinated people who were previously infected by COVID and received a single shot of mRNA vaccine after their infection, both showed a robust antibody response to variants.
This suggests that vaccines made to fight the original version of COVID-19 can boost a person’s immune response to a high enough level — a level that might require a booster shot to achieve or sustain — that it protects them against the virus in its different forms. That’s welcome news given that the viruses are always evolving and more variants bubble up. And it argues for focusing on vaccines that are less sensitive to changes in COVID’s genetic makeup.
“Chasing variants is not the race we’re going to win,” Veesler said. “We’re not going to be fast enough.”