The COVID-19 vaccine has offered most people the ability to return to their pre-pandemic lives. But people with weakened immune systems, such as transplant recipients and cancer patients, have had to remain vigilant because their bodies have not responded as robustly to the vaccine.
Now, new research may offer hope that a third dose of the vaccine could boost immunity for the roughly 10.5 million immunocompromised people in the United States, including those with autoimmune diseases.
“It may just be that their immune system just needs to see the proteins one more time in order to get to a level of immunity that people with more intact immune systems can accomplish with two doses,” said Dr. Dorry Segev, a professor at Johns Hopkins University School of Medicine.
A study published in the New England Journal of Medicine on Wednesday found that a third dose of the Moderna or Pfizer vaccine “significantly improved” its effectiveness in organ transplant recipients who take immunosuppressant drugs.
Doctors at Toulouse University Hospital in France assessed transplant recipients to see if a third dose boosted levels of the antibodies that fight COVID-19. Among the 59 patients who had no detectable antibodies after their second dose, 44 percent showed antibodies after their third. Among a second subset of patients who produced some antibodies after their second dose, all 40 exhibited increased levels after their third.
Lead author Dr. Nassim Kamar said this is the largest study in support of the hypothesis that three doses are better for organ transplant patients, adding, “I think it would be probably the same for all other immunocompromised patients.”
A smaller study, conducted by Segev at Johns Hopkins and published in Annals of Internal Medicine last Tuesday, had similar results. Among the 24 patients who had no detectable antibodies after their second dose, 33 percent showed an increase in antibodies after their third. All six patients who had low levels of antibodies after their second dose showed high levels after their third.
Segev called the results “incredibly exciting and encouraging,” and said the message is “one of hope” for immunocompromised individuals who didn’t respond after two doses.
In France, health officials have since April advised a third shot for the severely immunocompromised, including transplant recipients, dialysis patients, and some individuals with autoimmune diseases.
But third doses are not presently allowed in the United States. The Food and Drug Administration’s Emergency Use Authorization for coronavirus vaccines only permits individuals to receive one dose of Johnson & Johnson and two doses of Pfizer and Moderna.
Investigators at Johns Hopkins did not provide third doses to their study participants, Segev said. The patients obtained third doses on their own prior to the study. Some traveled to areas where there’s “less adherence” to federal guidelines, he explained.
Abigail Capobianco, a spokesperson for the FDA, said vaccine manufacturers must submit data attesting to the safety and effectiveness of a third dose before regulators will consider modifying dosage recommendations for immunocompromised individuals.
Dr. Robert Finberg — who led the vaccine trials for Pfizer at the University of Massachusetts Medical School — said the results are encouraging but emphasized it is early in the research process. He also cautioned against people trying to get a third dose of the vaccine without the supervision of a clinician.
For transplant patients, there are potential risks from the vaccine, including organ rejection, said Kamar, who recently published a case in Kidney International of a kidney transplant recipient who experienced organ rejection after her second dose.
“Our main concern is that when we boost the immune system several times, since we are dealing with organ transplant patients, we are a bit afraid of having accurate rejection,” Kamar said.
Aware of the risks, Segev hopes to launch a clinical trial later this summer to research the efficacy of third — and even fourth — doses, in controlled situations that will allow him to carefully monitor both the transplanted organ and the patient’s immune response.
“Everyone is cautiously optimistic that ultimately we will be able to find a way to reach protective immunity for the majority of immunosuppressed people in this country,” Segev said. “But . . . we really need to be careful to understand the risks of these kinds of vaccination strategies before unrolling them publicly.”
Some patients may simply never respond to the vaccine. Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, said there are always vaccine non-responders, even among individuals who are not immunocompromised.
“I do think that it’ll be difficult to get into 100 percent, but the fact that a simple third dose can raise good responses in one-third to one-half of previous non-responders is very encouraging,” he said.
Sam Dey, 52, who received a heart transplant in 2015, said that despite receiving two doses of Pfizer, his body has not produced the antibodies necessary to fight COVID-19. As a result, he is “living life as if the pandemic has just started.”
Dey is wary of the studies on third doses because of their small sample size and lack of diversity among participants. But he said he was glad to see there’s a chance he might someday be able to generate antibodies while on his immunosuppressive drugs: “There’s always hope.”
In the meantime, and sometimes even after they create antibodies, immunocompromised individuals need to continue to take health precautions.
Segev said he has been telling his transplant patients, “Get vaccinated but act unvaccinated;” that is, continue to wear a mask, keep 6 feet of distance, and follow all other recommendations that the Centers for Disease Control and Prevention has for the unvaccinated.
Glenda Daggert, 75, received a kidney and pancreas transplant in 1999 and got the vaccine as soon as she was eligible, but “kept being as cautious as ever.” It was only recently that Daggert found out that she is among the subset of transplant patients on immunosuppressive drugs who developed antibodies after two doses.
“I feel extremely lucky,” she said. “It was very relieving to get the confirmation.” Nonetheless, Daggert said, she is still wearing her mask indoors, and “very rarely” takes it off outdoors.
Her husband, Ira Copperman, the co-president of the Transplant Support Organization, said: “It’s safe to say that our community is going to continue to be pretty vigilant.”
Dr. Daniel Kuritzkes, an infectious diseases doctor at Brigham & Women’s Hospital, affirmed the importance of strict precautions for immunocompromised individuals.
That’s most applicable to individuals with the highest level of immunosuppressant drugs and the lowest level of vaccine response — cancer patients who are in active chemotherapy and all transplant recipients, including organ, stem cell, and bone marrow, said Kuritzkes.
Individuals on lower levels of immunosuppressant medicines to treat autoimmune diseases — such as inflammatory bowel disease, lupus, or arthritis — fall into a “gray zone” in how they respond to the vaccine, he said. “They really need to speak to their health care provider to get a sense of where on the spectrum of immunosuppression they may lie,” Kuritzkes said.
As for individuals who live with HIV, most can be “reasonably comfortable” that they will have a “good response” to the vaccine, particularly if they are on antiretroviral drugs, he said.
Camille Caldera was a Globe intern in 2022.Follow her on Twitter @camille_caldera.