Fourth Dose of mRNA-Based Vaccine May Produce Response for Kidney Transplant Recipients

These individuals also receive immunosuppressive drugs that often impair the immune responses to the vaccinations, study results show.

Results of a case series, published in Annals of Internal Medicine, show that a fourth dose of an mRNA-based COVID-19 vaccine produces a satisfactory antibody response in some individuals with kidney transplants who did not respond adequately after 3 previous doses.1

Individuals who received kidney transplants are also receiving immunosuppressive drugs that often impair the immune responses to mRNA vaccines, so those individuals are at high risk for severe disease during the pandemic, according to the study.2

The FDA has authorized individuals who are immunocompromised to receive a third dose of an mRNA vaccine after the standard 2-dose regimen, but about 50% of individuals who did not response after a second dose did not respond to a third dose.2

Investigators from the University Hospital of Strasbourg studied 92 individuals with kidney transplants at 3 independent French university hospitals. They investigated whether a fourth dose of an mRNA-based ani-SARS-CoV-2 vaccine would increase antispike IgG titers in individuals with kidney transplants who had a weak serologic response after 3 doses.1

The individuals, who had antispike IgG titers less than 143 BAU/mL 1 month after a third dose were given a fourth dose of an mRNA vaccine. Investigators took the measurement of antispike IgG titers, which correlates with the presence of neutralizing antibodies, 2 to 6 weeks later.1

They found no safety concerns with the fourth dose and said that after a median of 29 days, the median antispike IgG levels increased significantly to 145 BAU/mL from 16.4 BAU/mL. Approximately 50% of individuals reached the threshold of 143 BAU/mL.1

Those who did reach the threshold had longer intervals between their transplants and fourth vaccine doses. They were also less frequently treated with steroids.2

The percent of individuals who had antispike IgG titers above 143 BAU/mL after the fourth dose was about 48% for the BNT162b2 (Pfizer) vaccine and about 52% for the mRNA-1273 (Moderna) vaccine.2

Those who received the Moderna vaccine also had higher IgG titers, investigators said.2

Just 1 individual was diagnosed with mild COVID-19, and the individual’s antispike IgG level was 28 BAU/mL 1 month after their fourth vaccine dose.2

Investigators also said that in an unpublished study that individuals who received kidney transplants and had a previous COVID-19 infection had higher antispike IgG titers than uninfected individuals with kidney transplants who were vaccinated.2

Investigators did not examine the T-cell immunity of these individuals after repeated vaccine doses.2

They acknowledged that the increase of antispike IgG titers does not provide protection from infections and disease and encourage studies with a longer duration of follow-up to evaluate the risk of COVID-19 for individuals similar to those in this study after additional vaccine doses.2

References

1. A fourth dose of mRNA-based vaccine may be warranted in some kidney transplant recipients. EurekAlert. News release. January 10, 2022. Accessed January 11, 2022. https://www.eurekalert.org/news-releases/939695

2. Caillard S, Thaunat O, Benotmane I, Masset C, Blancho G. Antibody response to a fourth messenger RNA COVID-19 vaccine dose in kidney transplant recipients: a case series. Ann Intern Med. 2022; doi:10.7326/L21-0598.