A third of organ recipients who had no antibodies after their second dose developed them after a third dose, according to a small study reported Monday in the Annals of Internal Medicine. The researchers also found that participants with just a small rise in their antibodies after their two-dose regimens had higher levels after they got an added shot.

The results are suggestive only, coming from a 30-person observational study by Johns Hopkins University researchers. But they were eagerly awaited in a transplant community seeking to return to normal activities as the pandemic wanes. About 160,000 transplants have occurred in the U.S. since 2017.

“It’s showing us that the immune systems of immunosuppressed patients can be activated,” said Dorry Segev, one of the researchers and a professor of surgery and epidemiology at the university.

Earlier studies from the Johns Hopkins researchers showed transplant recipients, who must suppress their immune system with drugs so their bodies don’t reject donated organs, are less likely to develop antibodies after two doses of a messenger RNA vaccine, the type made by Pfizer Inc. and its partner BioNTech SE and by Moderna Inc.

Those findings spurred some patients to go to pharmacies and clinics on their own to get booster shots. The Johns Hopkins researchers then recorded the antibody levels in 30 of those patients to develop the latest data.

Further research should be conducted to determine the timing and conditions for a third shot and what options there may be for patients who don’t mount a response even after the third dose, Segev said by telephone.

Segev said his team is working with the U.S. Food and Drug Administration and National Institutes of Health to try to launch a clinical trial in the next few months in which researchers would be able to give patients a third dose in a controlled setting.

Side Effects

The FDA has said it needs data to evaluate alternate dosing regimens, and the Centers for Disease Control and Prevention does not recommend people take more than one vaccine series at this time. For transplant patients, there’s a risk when they take a new vaccine dose that they trigger their immune system in a way that could lead toward organ rejection, Segev said.

In the Johns Hopkins study, researchers didn’t observe any anaphylactic reactions or neurological complications. One heart transplant recipient experienced a rejection in which she has found to have antibodies directed against her donated organ a week after her third dose, but she recovered and it’s uncertain whether the rejection was related to the vaccine, Segev said.

A handful of patients have gotten or are considering a fourth dose, and the researchers are studying them as well, according to Segev. But if someone hasn’t mounted a response following a third dose, it’s unlikely they will after additional doses, he said.

Patients who don’t respond after a third dose may need to pursue other measures such as adjusting their immunosuppressive medication, but that can be dangerous for transplant patients since they risk organ rejection, he added.

Surrogate Use

Regulators have warned against using antibody tests as a measure of a vaccine’s effectiveness and as a means to assess immunity. Segev said that given Covid cases are low and immunocompromised people are taking precautions to avoid getting infected, studying the efficacy of vaccines in that population would be difficult, making the use of surrogates necessary.

Antibodies don’t show the entire picture of immunity and other arms of the immune system could help protect patients if they get infected. Segev’s team is also studying the cellular immune response of patients who got a third shot and confirming that their antibody levels after the third dose are correlated with neutralizing antibodies, he said.

Real-World Outcomes

Meanwhile, researchers at Virginia Commonwealth University have tried to determine how the findings on antibodies translate into real-world outcomes for transplant patients.

They found that out of 380 kidney recipients at their health system who have been vaccinated, seven got symptomatic infection, suggesting an early breakthrough rate of 1.8%. Four out of the seven were hospitalized and two of them required supplemental oxygen and treatments, according to research published in Transplant Infectious Disease in late May.

It’s promising that the breakthrough rate is low, but it is also higher than what’s been seen in the general population, said Chelsey Song, a transplant pharmacist who worked on the research. She recommends patients get vaccinated but still maintain social distancing and masking precautions.

There’s a lack of published data on the safety and efficacy of third shots, she said, and her transplant center is also hoping to start a clinical trial studying third doses for patients.