BY PAMELA FAYERMAN

A small B.C. study that offers an early glimpse into immune function after the first dose of a COVID-19 vaccine suggests changes to the current 120-day spacing between doses that B.C. instigated may be necessary.

While the National Advisory Committee on Immunization recently approved B.C.’s strategy to delay second doses four months in order to get more people vaccinated on a quicker timeline and to stretch out the supply of available vaccines, the new study suggests this long interval may be particularly risky for frail, elderly adults.

Early results from a B.C. group funded by the federal government to do the study shows that following a first dose of the Pfizer-BioNTech vaccine, long-term care (LTC)  residents had a much weaker response, versus a comparator group made up of healthcare workers.

The findings have been submitted for peer review and publication in the Canadian Medical Association Journal. Although it is a relatively tiny sample of 12 LTC residents, 18 healthcare workers (HCW) and four HCW who got first shots after they already recovered from COVID-19, it confirms concerns that the frail elderly in particular likely need second doses on a tighter timeline. About 31,000 LTC residents in BC have received their first doses but it’s believed only a tiny proportion of those have received second doses.

After one dose, the LTC subjects in the study had four times lower antibodies compared to HCW and laboratory analysis of the antibodies showed they were less effective at blocking COVID-19.  Contrast that with HCW who had already recovered from COVID but who also got a shot; they had seven to 20 times the antibodies compared to LTC residents, suggesting they may not need a second dose at all, according to co-author Dr. Marc Romney.

He is a clinical associate professor in University of British Columbia’s department of pathology and laboratory medicine, and is also medical leader for medical microbiology and virology at St. Paul’s Hospital/Providence Health Care.

In an interview Friday, Romney said across populations, there is “tremendous variability” in immune functions so that has to be taken into consideration when deciding whether to lengthen or shorten intervals between vaccine doses.

“We’ve been lacking these kinds of immune system studies until now, in order to assess risks. But now we are able to start gathering as much information as possible. The numbers in this first study are admittedly small but the finding is important. There is a consistently blunted response in the frail elderly and in this third wave of the pandemic, the situation is unstable. There are more hospitalizations and more variants and as one of the health professionals on the frontlines, I can tell you we are seeing the devastating impact of these variants, especially the P1 (Brazilian).”

Provincial Health Officer Dr. Bonnie Henry was one of the first in B.C. to receive a first dose of the Pfizer-BioNtech COVID-19 vaccine on Dec. 22, 2020. She recently said she will wait longer for her 2nd dose.

At a press briefing yesterday, Dr. Bonnie Henry, B.C.’s chief provincial health officer, appeared to downplay the study, pointing to “very mild illness” among those who got COVID even after being immunized.

She said the new study only looked at 18 people. It actually included 34.

“Looking at antibodies in 18 people doesn’t change our management when we have other studies that have shown us that there is still a very high level of protection overall,” she said. “And we do need to focus our attention on getting as many people that higher level of protection from a single dose right now.”

Romney said he agrees with extending the interval beyond the 21 days in the Pfizer clinical trials. “But it’s not a one-size-fits-all solution. It needs to be more nuanced, taking into consideration age and fragility. We know that there is a more blunted immune response in the elderly so it’s a bit risky to delay second shots and that includes people in long-term care or those who are also vulnerable but living in the community.

“There is also a psychological component that has an effect on mental and physical health,” he said, referring to the anxiety and stress many people experience when their booster shots are delayed.

There are now 150 participants in the ongoing research which will look more deeply into various immune system markers like T cells.

He said it’s near-impossible at this point to know how many antibodies and other immune system markers individuals need to mount a successful attack after a COVID exposure or infection. Every immune system is unique.

“The slightest attack on one individual’s immune system can have a devastating impact while in another, it may be slight. That’s why there’s a historical precedent for treating older people differently when it comes to vaccines. They get vaccines with adjuvants, for example, to boost the effect of influenza vaccines.

“The booster dose is like calling in the cavalry.”

Not only did the long-term care residents produce lower levels of antibodies than HCW after the first dose, but the antibodies they did produce were also less adept at blocking the SARS-CoV-2 virus from binding to its target cells.

“The antibody response was actively triggered in young, healthy people following a single dose of vaccine, while the response was clearly not as robust in older individuals. This indicates that some older people − not only in long-term care but also in the community − may be incompletely protected after their initial dose,” said Romney who collaborated with Dr. Zabrina Brumme at the B.C. Centre for Excellence in HIV/AIDS and Dr. Mark Brockman at Simon Fraser University.

The study is available on a pre-print basis on medRxiv. Dr. Tim Evans, executive director of the COVID-19 Immunity Task Force, which funded the study said evidence from Canada and the U.K. shows that older individuals are well-protected “for many weeks by a single dose.”

“Nevertheless, these findings are a reminder that there may be limits to how long we can stretch the time between doses for seniors and other segments of the population.”

As of today, 637,000 vaccines had been administered in B.C., of which just over 87,000 were second doses.

Henry has offered assurances that there is active surveillance of COVID activity in all populations and “if we start to see a decrease in real-world protection, in vaccine effectiveness in elderly people, then we will speed up second doses for that group of people.” But she also hinted she is flirting with delaying second doses even longer.

She said it may be that a booster dose is most effective if given even later, five or six months after the first dose for healthy individuals.

“That may give us longer-lasting protection that will take us through next year’s respiratory season now that we believe that coronavirus is going to be with us for a while,” she said.

In the U.S., federal health experts like Nancy Messonnier are resistant to the notion of extending dosing intervals. “We have to stick with what we know works,” she said in a virtual chat with STAT journalist Helen Branswell.

“This is the regiment that’s carefully studied. We’ve promised the American public that we would follow the data and follow the science and that’s what we’re doing.”

Branswell has also interviewed medical experts who believe delayed boosters will foster incomplete protection, giving rise to vaccine-resistant forms, also known as escape mutants. Paul Bieniasz of Rockefeller University said:

“My concern, as a virologist, is that if you wanted to make a vaccine-resistant strain, what you would do is build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection.

“You are essentially maximizing the opportunity for the virus to learn about the human immune system. Learn about antibodies. learn how to evade them,” he told Branswell.

pamela@medicinematters.ca

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