With the standard two-dose regimen of the mRNA vaccines, half of transplant patients don’t produce any detectable antibody response, and even those who do show some antibody response have, in general, lower levels of antibodies than the general population. In addition, clinical protection for vaccinated transplant patients is much lower: A fully vaccinated transplant patient has an 82-fold higher risk of getting a breakthrough infection, and a 485-fold higher risk of getting a breakthrough infection associated with hospitalization or death, than the general fully vaccinated public.

Other immunosuppressed populations also have decreased responses to the vaccines, although the amount of the decrease varies by the medications they take and the condition they have.

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The proactive approach that the FDA is taking by authorizing booster vaccinations for the immune compromised is very welcome news. So far there have been somewhat limited data about booster shots—meaning an extra dose of the same or a different vaccine beyond the currently authorized vaccination schedule—but emerging evidence seems to suggest that they can strengthen or achieve immunity in patients who are immune suppressed and who generally have a lesser chance of mounting an immune response. This includes patients after a solid organ transplant, certain types of cancers, especially blood cancers, and certain types of cancer treatments that impair the immune system. The limited data in patients with solid organ transplants or certain cancer types, for example, might suggest that the booster shot converts 20-40% of patients from an antibody negative test to a positive one—meaning the patients have at least some detectable level of immunity by a lab test after their booster shot. In addition, booster shots in these studies have been overall just as safe as vaccinations otherwise. Questions remain about whether booster shots work for all patients or if some patients have such a low chance to respond to the additional shots that they need other methods of protection, as well as whether a mix and match strategy might work better—meaning getting a different type of a booster vaccine than the original series.

Our study shows that in organ transplant recipients, a third dose of the Moderna mRNA vaccine was significantly better than a placebo for improving patients’ immune response. Organ transplant patients have a very poor response to the standard two dose regimen of COVID-19 vaccines. With a third dose, as compared to placebo, patients in our study had increased antibodies against the spike protein, as well as neutralizing antibodies, which serve to prevent viral infection, and T-cell responses, which limit severity of infection. Ours is the first study to include a placebo group for comparison with the group receiving a booster shot, which is very important to demonstrate the efficacy of an intervention. Based on the results of this study, we believe that a third dose should be recommended for organ transplant patients. The results may also be applicable to other groups of immunocompromised patients such as cancer chemotherapy or bone marrow transplant recipients, but we encourage further studies in those groups.