‘This gives hope’: A third COVID-19 vaccine dose can boost protection for organ transplant recipients | Science

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By Jennifer Couzin-Frankel

scienceThe COVID-19 reporting of is supported by the Heising-Simons-Stiftung.

A few months ago, transplant surgeon Dorry Segev was desperate about how COVID-19 vaccines would work in patients like him who have a donated organ and are taking potent drugs to suppress their immune systems. After a dose of a potent messenger RNA (mRNA) vaccine, for example, only 17% of these patients produced protective antibodies against the coronavirus pandemic and beyond the two standard doses, only 54% did. The drugs his patients took to protect their transplanted organ prevented them from building a healthy immune response after vaccination. Even people who made the antiviral antibodies often had very low levels, which raised questions how well they were shielded from COVID-19.

But now Segev at Johns Hopkins University has become cautiously optimistic. He and his colleagues have found that a third dose of vaccine can help: Among 24 organ transplant patients who no longer had antibodies after two doses, eight people produced protective antibodies after picking out a third one on their own. Six people who had few antibodies against the coronavirus after two doses all had high levels after a third shot, the researchers reported in the today Internal Medicine Annals. Although Segev did not conduct a systematic study – the 30 patients were given combinations of different vaccines at varying intervals – “this gives hope that is critical at the moment,” he says. “There is some encouraging evidence that we can help the immune system do what it needs to do.”

Organ transplant recipients are participants in a research project that Segev and his colleagues are conducting to study COVID-19 vaccine responses in people with compromised immune systems. In this case: “We just got emails from people saying, ‘Hey, I’m getting a third dose, do you want my blood?'” Says Segev. He took the opportunity. (In the United States, even with mRNA vaccines currently approved, determined individuals can secure additional doses with just two doses of vaccine.)

Segev’s study is the first to report results after a third dose of vaccine, and it is part of a wider discussion of whether and when to offer additional doses to those at risk. In France, health officials recommended a third dose to all organ recipients in the country in April. Because of this policy shift, 383 kidney transplant recipients at Strasbourg University Hospital received a third dose of Moderna’s mRNA vaccine and doctors have antibody results for 184 of them. Although the results are not yet published, they roughly agree with Segev’s small cohort: 28 percent of French patients who showed no antibodies after two doses developed them after the third injection and 82% who had a poor response after two injections a stronger reaction after the third, says Sophie Ohlmann, a nephrologist at the hospital.

There are about 500,000 people in the United States who have had organ transplants, but they’re not the only ones concerned about how well the vaccines will work for them – others include people with autoimmune diseases and people with cancer who received COVID-19 vaccines while their immune systems were suppressed by chemotherapy. “I wouldn’t be surprised to see higher doses work, but we have to do it systematically and find out,” said Deepali Kumar, director of transplant infectious diseases at Toronto General Hospital.

She argues that third dose clinical trials are critical to clarifying the ideal timing and potential risks in vulnerable populations. One of their concerns is whether an extra dose of the vaccine, which boosts the immune system, could result in rejection of a donated organ; In Segev’s study, a heart transplant patient had a mild episode of rejection 1 week after her third dose, although doctors can’t tell if this was related to the extra dose. She recovered without incident.

Kumar expects results in July from a clinical study she is conducting on 120 transplant patients, only about a third of whom had antibodies after two doses of Moderna’s vaccine. In the study, half of all participants received a third dose 2 months after the second injection, the rest received a placebo injection.

In Germany, 11 centers conducting a COVID-19 vaccine study are recruiting volunteers with a range of conditions that by their nature or medication may affect immune function, including people with organ transplant or autoimmune diseases and dialysis patients. After the second vaccination dose, the researchers will examine antibodies and T cells and possibly offer some participants a third vaccination dose, says Leif Erik Sander, an expert on infectious diseases at the Charité in Berlin, who is leading the work. And Segev is in talks with the National Institutes of Health to start a study of transplant patients this summer.

“We have strong biological rationale for a third dose in certain populations,” said Ravi Parikh, health policy researcher and medical oncologist at the University of Pennsylvania. His patients haven’t asked him about the third dose yet, but he imagines he supports this strategy for some.

When it comes to cancer patients, Parikh isn’t too concerned about the effectiveness of two doses. Last month a study in JAMA oncology reported that 90% of a group of cancer patients Chemotherapy and other drugs produced antibodies after two doses of Pfizer’s mRNA vaccine. (Parikh co-wrote a comment accompanying this paper.) Another study in Cancer cell reported that this month 94% of 200 cancer patients had antibodies after vaccination. Those numbers are “excellent news,” says Salomon Stemmer, a medical oncologist at Tel Aviv University who does the JAMA oncology Study.

But in Stemmer’s cohort of 102 patients in treatmentAntibody levels ranged from a quarter to a third of healthy family members after receiving a vaccine. The difference doesn’t worry Stemmer too much, but because the levels of SARS-CoV-2 antibodies naturally decrease over time, he wonders whether they may drop worryingly low earlier in cancer patients because they assume a lower level. Parikh agrees that this is a big question: “We don’t know how quickly these antibody titers will go down,” he says.

Stemmer continues to follow his cohort and plans to test antibody levels every 2 to 3 months. He also wants to learn more about the small group of patients who have not produced any antibodies against SARS-CoV-2 at all: Including three women with breast cancer who are receiving “dose-dense” chemotherapy, which means less time between treatments. In some cases, third doses of the vaccine might help, but Stemmer says he would only offer them as part of a clinical trial.

Segev hopes more information will be available soon to help these populations. Right now, he admits, “There is a lack of leadership and knowledge.” Meanwhile, Segev admits that some people prefer to take matters into their own hands, while others would eagerly participate in a clinical trial – although he did urges anyone considering a third dose of the vaccine to speak to their doctor first. “Whatever happens out there, we’ll learn as much as possible,” he says.

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