Fourth Vax Dose Not the Charm for Organ Transplant Recipients

Solid organ transplant recipients exhibited suboptimal immune responses to Pfizer’s COVID-19 mRNA vaccine, even after four doses, a small French study found.

All 37 patients examined had low neutralizing antibody titers and cellular responses, and those with no detectable immune response after the third dose did not appear to mount one after the fourth dose, reported Nassim Kamar, MD, PhD, of Toulouse University Hospital in France, and colleagues in JAMA Network Open.

In August, CDC recommended that solid organ transplant recipients receive an additional dose of Pfizer or Moderna vaccine, and in October they added that “moderately or severely immunocompromised” people may receive a fourth dose of any authorized COVID vaccine at least 6 months after their third dose.

Kamar’s group noted that prior research showed neutralizing antibodies were detected in 70% of solid organ transplant recipients after a third dose.

They examined 37 solid organ transplant recipients from July to August of this year. Of these, 31 had no response after the third dose of vaccine and five had a “weak” response. The first two doses of Pfizer vaccine were given a month apart, the third a mean of 57 days later, and the booster a mean of 65 days later.

Mean age of patients was 60, and 54% were men. Anti-SARS-CoV-2 antibodies were detected in five patients prior to the fourth dose, and in 18 patients a month later.

Of the 31 patients who were seronegative after the third dose, 13 became seropositive 4 weeks after the fourth dose. Not surprisingly, antibody concentrations were significantly higher among patients with a detectable response versus no response prior to the fourth dose, but neutralizing antibody titers a month after the fourth dose “did not differ between responders and non-responders to [three] doses,” the authors wrote.

A month after the fourth dose, 32 of 37 patients had antibody concentrations less than 140 BAU/mL, which Kamar’s group defined as “a threshold providing 12.4% protection among healthcare workers,” and all 37 patients had neutralizing antibody titers less than 64 IU/mL.

Among the examined patients, there were no serious adverse events or acute rejection. Four patients experienced fatigue and myalgia, one had gastrointestinal symptoms, and one kidney transplant recipient had “a recurrence of IgA nephropathy.”