3rd COVID-19 vaccine dose increased protection in transplant patients, study shows

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Mike Willis was intrigued when he heard about a study aimed at determining the effectiveness of third-dose COVID-19 vaccine boosters for organ transplant recipients.

As a heart transplant patient who takes immune-suppressing medication every 12 hours, Willis said the chance to potentially boost his protection against COVID-19 made it easy for him to volunteer.

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“I had zero antibodies after two doses,” said the 66-year-old, adding he was delighted to learn the double-blind study had given him a third dose instead of a placebo. “So anything (is) higher than nothing.”

Researchers at the University Health Network who led the study say findings released Wednesday suggest a third-dose booster is the “best way to increase protection” in transplant recipients.

And as the highly transmissible Delta variant drives cases in parts of the country, they say there’s more urgency to ensure transplant patients, who often don’t mount a sufficient immune response with a normal two-dose series, can augment their protection.

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“As I see it, there are transplant patients that are completely unprotected right now, even though they’ve had two doses,” said Dr. Deepali Kumar, director of transplant infectious diseases at UHN and joint-senior author of the study.

“If we can offer them a third dose to have a better chance of protection, I believe we should.”

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The study, published in the New England Journal of Medicine, looked at levels of different types of antibodies as well as T-cell responses in 120 transplant patients in Ontario and found increases in the majority of those who received a third vaccine dose.

UHN said the study is the first randomized placebo-controlled trial of COVID-19 boosters in transplant patients. Researchers compared 60 participants who received a third shot of the Moderna vaccine to 60 who got a placebo.

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Previous studies, including one from the United States earlier this summer, suggested third doses could amplify immune responses in some transplant patients but did not include a control group.

“It’s really hard to know if something’s working unless you do that,” said Dr. Atul Humar, the medical director of the Ajmera Transplant Centre and the study’s other joint-author.

“We had seen data that maybe there was a benefit, but I think this is the definitive study which shows a clear benefit.”

Ontario’s Ministry of Health said Wednesday it would “continue to actively review the evidence and provide updated guidance as required.”

'Great immune response'

All participants in the study were fully vaccinated with Moderna and none had previous COVID-19 infections. Half of the participants received a third Moderna shot two months after their second dose.

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Just over half, or 55 per cent, of those who received a third dose saw their antibody response rate reached at least 100 units per millilitre, compared to 18 per cent for the placebo group.

Kumar said previous modelling suggested 100 units “might be protective.” In healthy people, antibody levels after two doses typically reach 1,000 to 10,000 units per millilitre, Kumar said, and some of the transplant study participants showed similar numbers.

“So that was actually very exciting,” she said. “We were able to get a great immune response with a third dose.”

Kumar added that those who didn’t reach the 100-unit benchmark could still have boosted protection following a third dose.

The study also found 60 per cent of the three-dose group developed neutralizing antibodies that help identify the COVID-19 virus. T-cell responses, which help the immune system prevent severe disease, were also more robust in the three-dose group.

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Kumar said only mild side effects were reported with the booster.

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Moderna was chosen because the vaccine has a higher dose than Pfizer-BioNTech’s, Kumar said, adding that previous studies from flu shot effectiveness suggested a higher-dose influenza vaccine was more successful in transplant patients.

She said more studies would be needed to see how Pfizer recipients respond. A national study by the same UHN team will look at blood samples of transplant patients who received either Pfizer or Moderna as their third dose.

“I think theoretically (Pfizer) would have a similar response but it would be hard to say without a head-to-head comparison,” Kumar said.

While Willis’ antibody levels rose significantly after his third Moderna shot, he said he likely isn’t as fully protected as a healthy person with two doses.

Willis acquired his new heart in 2015 after he developed myocarditis, a scarring of the heart muscles, following a previous viral infection. He’s had to be careful about exposing his weakened immune system to pathogens since.

The retiree from Guelph, Ont., said he still follows the usual safety measures like physical distancing and mask-wearing, especially indoors with strangers. But when he’s with people he knows who are fully vaccinated, he can feel more at-ease.

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Like many transplant patients, Willis relies on those around him to get vaccinated themselves to lessen the chance he’ll be exposed to the virus.

“If it wasn’t for that I might be a hermit,” he said.


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