Third Dose Boosts Post-Transplant COVID Vaccine Immunity

A third dose of COVID-19 vaccine sparked the desired immune response for a substantial proportion of transplant patients but still left some unprotected, a French series showed.

Among the first 101 consecutive solid-organ transplant recipients treated after French regulators recommended a third dose for immunosuppressed patients, the proportion with antibodies went from 40% before that dose to 68% 4 weeks after it.

For those seronegative for antibodies before the third dose, 44% were seropositive 4 weeks after that dose (26 of 59), Nassim Kamar, MD, PhD, of Toulouse University Hospital in France, and colleagues reported in a research letter in the New England Journal of Medicine.

Patients who still didn’t have an antibody response tended to be older and to have lower immune cell counts and poorer kidney function than patients who had an antibody response.

No patients lost seropositivity with the third dose or had a serious adverse event or an acute organ rejection episode.

“I think this is a nice confirmation of what we found,” said Dorry Segev, MD, PhD, of Johns Hopkins University in Baltimore, citing the series his group recently reported in the Annals of Internal Medicine.

In that series of 30 U.S. patients with low or no antibodies after their second vaccine dose, the third dose was likewise safe and got all of the initially low-positive patients to high antibody titers and a third of the initially-negative patients to at least low-positive titers.

One of the patients in Segev’s series had a mild rejection episode 1 week after the third dose, although causality wasn’t clear.

“One major thing that is missing from the current evidence is risk to the transplanted organ in the context of the immune activation from the third dose — such as development of donor-specific antibodies or sub-clinical injury,” Segev told MedPage Today.

He argued that even this larger series from France shouldn’t spur routine third-dose vaccination for immunosuppressed patients. “Until we better understand the risks in addition to the benefits, approaches such as third doses are best studied under research protocols,” he said.

The French cohort comprised the first 101 consecutive solid-organ transplant recipients given three doses of the Pfizer COVID-19 vaccine under the French National Authority for Health’s recommendations. The group was dominated by kidney recipients (78), with an average of 8 years between transplant and vaccination. The first two vaccine doses were given 1 month apart, and the third dose was administered 61 days after the second dose.

In Segev’s study, patients had gotten standard two-dose mRNA vaccination and then the third dose was another mRNA vaccine dose for about half whereas the other half received the Johnson & Johnson adenovirus vaccine.

None of the patients in either series developed COVID-19 after their third dose, although the duration of follow-up remains limited.

What to do about persistently low or negative antibody levels after a third vaccine dose isn’t clear.

“Barrier measures should be maintained, and vaccination of the relatives of these patients should be encouraged,” Kamar’s group concluded.

Such patients likely would need some sort of modification of their immunosuppression regimen in order to achieve vaccine-mediated antibody responses, Segev noted. “However, those really take risk to the next level, and should be done under very careful protocols with close monitoring of the transplanted organ.”

His group has an ongoing observational study of third dose vaccination but also hopes to soon begin enrolling a clinical trial.

Whether the vaccines will eventually require a booster shot among people with competent immune systems is also being closely watched, with some speculation that additional doses may be needed on an annual basis.