Booster dose could make transplant recipients less vulnerable to COVID-19, study finds
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Past research has shown that solid organ transplant recipients do not respond as well to COVID-19 vaccines as others. Researchers from Johns Hopkins found that a booster dose could make them less vulnerable to infection.
In a new study published in Annals of Internal Medicine, William A. Werbel, MD, an infectious diseases fellow at Johns Hopkins School of Medicine, and colleagues reported that a third dose of COVID-19 vaccine increased antibody levels in a third of patients who had negative levels and all patients with low-positive antibody levels after two doses.
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“We have conducted a national vaccine registry for the past 6 months to rapidly study safety and antibody responses of COVID-19 vaccines in thousands of patients with compromised immune systems, such as organ transplant patients,” Werbel told Healio.
“We found that nearly half of all transplant patients produced no antibody against the key viral protein in the authorized vaccines — anti-spike antibody — in contrast to very high levels in almost all healthy persons in the clinical trials,” Werbel said. “This, coupled with reports of breakthrough infections after vaccination and the fact COVID-19 can be very serious in transplant patients, has prompted worldwide interest in strategies to improve the immune response to these otherwise highly effective vaccines in the hope of providing greater protection for vulnerable patients.”
According to Werbel, the strategy of using an a booster dose had not been studied thoroughly in any population.
“Once vaccine supply improved in the United States, hundreds of transplant patients who had suboptimal antibody responses after the two-dose messenger RNA vaccine series have independently sought out third doses of COVID-19 vaccines,” Werbel said. “Many have reported this to us, volunteering to donate blood before and after a third shot for antibody testing and to report to us if they had any reactions or other adverse outcomes in the week after vaccination.”
Werbel and colleagues studied 30 organ transplant recipients who reported receiving a third dose of vaccine between March 20 and May 10, 2021. None of the patients reported an illness before vaccination that was consistent with COVID-19 or had a positive PCR test.
During the initial vaccination, 57% of the 30 patients received two doses of the Pfizer/BioNTech vaccine and the rest received two doses of the Moderna vaccine. All patients were tested for anti-spike antibodies a median of 9 days before they received a third dose. Results of these tests showed that 24 patients had negative antibody levels and six patients had low-positive antibody levels, Werbel and colleagues said.
Patients received their third dose a median of 67 days after the second — 15 patients received the Johnson & Johnson shot, nine received the Moderna vaccine and six received the Pfizer/BioNTech vaccine. The researchers repeated antibody testing a median of 14 days after the third dose and found that, among the six patients with low-positive antibody levels before dose three, all had high-positive antibody levels after dose 3. However, of the 24 patients with negative antibody levels before dose three, only six of the 24 had high-positive antibody levels after the third dose. Of these, two had low-positive antibody levels and 16 (67%) remained negative.
Werbel and colleagues also surveyed 23 patients 7 days after the third dose and asked about specific vaccine reactions. Fifteen said they felt mild or moderate local reactions and one reported severe arm pain. The most common systemic reaction was mild or moderate fatigue, followed by severe headache and severe myalgia. No patients reported fever, anaphylactoid reactions or neurological complications, according to the researchers.
“Third dosing of COVID-19 vaccines appear to boost anti-spike antibody responses in about 50% of transplant recipients in this preliminary series, particularly those who had preceding low-positive results after a standard two-dose mRNA vaccination,” Werbel said. “Patients with negative antibodies after standard vaccination, however, were less likely to show a boosted antibody response and were generally lower when elicited. Booster dosing may be a viable option for certain transplant patients as a means to improve antibody responses and, thus, possibly better protection from COVID-19.”
Perspective
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SARS-CoV-2 vaccination following solid organ transplantation has become a thorny issue. Anywhere from 40% to 60% of transplant recipients have no detectable spike protein antibodies 2 weeks after a full vaccination series. Although this report is a small observational convenience sample, it provides a good proof of concept that some patients may indeed respond after one additional vaccine dose and that the side effect profile was not unexpected. However, the work to gather and interpret additional data from ongoing studies is just beginning. Modification of immunosuppression (eg. mycophenolate) and giving different vaccine types could perhaps increase the probability of a response. Measuring additional markers of immune response such as T cells could provide reassurance in some. Additionally, drawing from the hepatitis B vaccine revaccination playbook in transplant recipients, a higher vaccine dose and additional rounds of boosters may be needed for nonresponders. As we reopen society in the U.S. in the face of a large burden of COVID-19 globally, these questions couldn’t be more timely for transplant and other immunocompromised patients, their clinicians and their loved ones.
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