Third COVID-19 vaccine dose effective and safe for transplant recipients: study

TORONTO -

A third dose of COVID-19 vaccine provides substantially more protection against the coronavirus in transplant patients, providing hope for other immunocompromised individuals, according to a world-first study.

The randomized, placebo-controlled clinical trial, considered the gold standard in medical research, sought to determine whether a booster shot – in this case the mRNA vaccine by Moderna – would be effective and safe for transplant recipients.

Transplant recipients are particularly vulnerable to infectious diseases, such as COVID-19, because their immune systems are typically unable to mount an adequate response to immunization – depending on the degree of immunosuppression and the amount of time since their transplant.

“We know that transplant patients are immunocompromised and they don’t respond to two doses of the standard COVID vaccine,” Dr. Deepali Kumar, the director of transplant infectious diseases at University Health Network and joint-senior author of the study, told CTV News.

“So we decided to do a trial where we looked at a third dose of COVID vaccine to see if we could boost immunity.”

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To do this, the researchers enrolled 120 transplant patients between May 25 and June 3 who had never had COVID-19 and who had previously received two doses of the Moderna vaccine. Half of the participants received a third dose of the Moderna vaccine, while the other half received a placebo dose two months after their second doses.

To measure the booster’s effectiveness, they measured the level of antibodies in the two groups to see if they obtained an antibody level strong enough to protect against the spike protein of the virus.  

According to the results, the placebo group’s response rate was only 18 per cent, while the Moderna three-dose group had a response rate of 55 per cent.

In addition to studying the groups’ antibody levels, the researchers also looked at the effectiveness of neutralizing antibodies – the antibodies that neutralize the virus. They found that only 25 per cent of the patients in the placebo group developed these neutralizing antibodies compared to 60 per cent in the Moderna group.

While antibodies protect against infection, the immune system also employs T-cells to prevent severe disease, which is why the UHN scientists also examined the differences in T-cell response between the two groups of participants.

They found there was a “substantial” improvement in the ability of the Moderna group to develop a robust T-cell response against the coronavirus. 

“If you have both antibodies and T-cells, you’re protected from severe infection and from actually contracting the infection. You’re protected from both,” Kumar said.

Along with showing a positive response in both arms of the immune system – the antibody arm and T-cell arm – the trial also proved the third dose of COVID-19 vaccine was safe for transplant patients.

Kumar said the third dose of Moderna was well-tolerated with patients experiencing only mild side effects, such as fever. The researchers also said the booster didn’t cause acute organ rejections, which was a concern for repeated vaccinations in transplant recipients.

Although Moderna’s vaccine was used for this specific trial, Kumar said the results could potentially apply to other mRNA vaccines, such as Pfizer. She said she would be careful, however, about applying them to other vaccine types.

In light of the findings, Kumar said medical practitioners should change their practice when it comes to vaccinating transplant patients against COVID-19.

“We need to be giving three doses of vaccine to transplant recipients, as opposed to the usual two doses in order to complete that primary vaccine series,” she said.

Kumar expressed confidence in their results thanks to their use of a placebo in the clinical trial, which she said makes the study more “robust.”

“I think we've definitively shown that the third dose does benefit transplant recipients.”

That’s welcome news to Mike Willis, a heart transplant patient in Guelph, Ont. who received a third dose of Moderna as part of the clinical trial.

“I’m hopeful that if I was to catch something … I am finally a little bit better protected,” he said.              

What’s more, Kumar said their findings might have broader implications for other immunocompromised groups, such as patients with cancer, lupus, and Crohn’s disease, who don’t get enough protection from two doses of COVID-19 vaccine. However, she said they would need specific studies in those populations.

Marie Josee Lafleur from Val-des-Monts, Que., lives with inflammatory bowel disease and finds the new study hopeful. Those with autoimmune disorders often use the same immune-suppressing medications as those who have had organ transplants.

She told CTV News that research out of the United Kingdom suggests that even if she and others in her situation do develop antibody protection after their second dose of a COVID-19 vaccine, it will wane after a few months.

"I have been adopting the approach that I'm still not vaccinated, because there is no guarantee that I'm protected with two doses," she said.

Lafleur plans to ask her doctor if the new data on third doses might allow her to get a COVID-19 booster shot.

Dr. Sita Bhella, a cancer doctor at UHN, said that further research is needed before applying the findings of this study to other patient groups.

“This study offers hope that a booster may improve immune responses in high-risk populations, such as those with cancer. Further study is needed, but this brings us all one step closer to our patients returning to pre-COVID lives, such as being able to babysit their grandkids without fear and anxiety,” she said.

It is also not yet clear if the new findings apply to all transplant recipients. Dr. Julie Ingelfinger, a Boston-based nephrologist who co-wrote an editorial that accompanied the study, described the conclusion as "a very solid hint" and said that it could have implications for where doses are sent and how the immunocompromised are prioritized relative to residents of countries where vaccines have been harder to come by.

"People have been really eager to see data like this, and it is encouraging data," she told CTV News.

The study was published in the New England Journal of Medicine on Wednesday.