Testing Third Doses of COVID Vaccine in Transplant Patients

Last month, we reported in JAMA and here in MedPage Today that almost half of transplant patients show no antibodies after a full two-dose mRNA SARS-CoV-2 vaccine series. We’ve also recently published that the antibody response is no better, and possibly even worse, with the single-dose Johnson & Johnson adenovirus vaccine. Combined with reports of breakthrough COVID-19 infections in fully vaccinated transplant patients, these findings are understandably frightening and frustrating to the patients we take care of as transplant doctors. While people with competent immune systems are starting to catch glimpses of life as it was pre-pandemic, transplant patients are lamenting the need to continue protective behaviors like mask-wearing and social distancing.

How are we going to solve the problem of suboptimal vaccine response in transplant and other immunosuppressed people? One possibility is a third vaccine dose to boost the immune response. MedPage Today recently reported a case study of one transplant surgeon, who is also a transplant recipient, who carefully considered the risks and ultimately found an antibody response in this approach. But is this generalizable to all transplant patients?

We have published a new study of the safety and antibody responses for 30 transplant patients who received a third dose of SARS-CoV-2 vaccine. These patients started with either low antibodies (20% of study participants) or no antibodies (80% of study participants) following standard two-dose mRNA vaccination. They then received a third dose of one of the three available vaccines in the U.S.: about half received another mRNA vaccine and half received the Johnson & Johnson adenovirus vaccine.

The good news is that all six patients who had low-positive antibodies after two doses successfully boosted their antibodies to high-positive after a third dose, finally reaching levels more comparable to those seen in immunocompetent persons. Even among those who had no antibodies to begin with, one-third produced an antibody response after a third dose. The third dose generally appeared safe, with most people experiencing mild to moderate arm pain or fatigue, similar to that seen in the standard vaccine trials. One heart transplant patient did have evidence of mild organ rejection a week after the third dose, but it was not clear if this was related to vaccination.

Our findings are encouraging, and provide hope for our immunosuppressed patients: boosting immune responses might be achievable. However, there is still a lot to learn. It is not yet clear which combination of vaccines is most likely to provide higher antibody levels, whether some patients will require immunosuppression modulation to achieve higher antibody levels, and whether antibody levels will correlate with real-world protective immunity. It is also not fully established if the immune activation with a third dose will negatively impact the transplanted allograft.

We will continue to explore these questions in our ongoing observational study for which enrollment remains open. We also hope to start enrolling patients this summer into an interventional trial that will provide third dose administration in a controlled and standardized environment.

William Werbel, MD, is an infectious disease physician at Johns Hopkins University School of Medicine. Dorry Segev, MD, PhD, is a professor of surgery and epidemiology and associate vice chair of surgery at Johns Hopkins University School of Medicine and Bloomberg School of Public Health.