Antibody response to a fourth dose of COVID-19 messenger RNA vaccine in kidney transplant recipients: a case series
Fund: Kidney transplant recipients receiving immunosuppressive drugs have an altered immune response to COVID-19 messenger RNA (mRNA) vaccines (1). Therefore, despite standard vaccination with mRNA vaccines, many of these patients remain at high risk for serious illness during the current pandemic. The U.S. Food and Drug Administration cleared immunocompromised people to receive a third dose of mRNA vaccine after the standard 2-dose regimen to further enhance protection, and French health officials approved a third dose on April 11. 2021. Subsequent studies found that approximately 50% of patients who did not respond after a second dose seroconverted after a third dose, resulting in an overall seroconversion rate of approximately 65% (2, 3). Antispike IgG titers greater than 143 binding antibody units (BAU) per milliliter correlate with the presence of neutralizing antibodies (the most widely accepted marker of disease protection) against wild-type virus and alpha, beta and gamma variants, but neutralization of the delta variant requires higher titers of antispike IgG (4). Therefore, patients with low titers of antispike IgG may remain insufficiently protected. In June 2021, French health authorities approved the offer of a fourth dose of vaccine to solid organ transplant recipients who had a poor response after a third dose.
Goal: To examine whether a fourth dose of a mRNA-based SARS-CoV-2 vaccine would increase antispike IgG titers in kidney transplant recipients who showed a poor serologic response after 3 doses.
Case report: A fourth dose of mRNA vaccine (BNT162b2 [Pfizer], m = 34; MRNA-1273 [Moderna], m = 58) was administered to 92 kidney transplant recipients from 3 independent French university hospitals (Strasbourg, Lyon and Nantes) who had antispike IgG titers less than 143 BAU / mL 1 month after a third dose. All had measurements of antispike IgG titers 2-6 weeks later (median, 29 days [interquartile range, 26 to 34 days]). The table presents the characteristics of these patients.
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There were no safety concerns with the fourth dose of vaccine. After a median of 29 days, the median levels of antispike IgG decreased from 16.4 BAU / mL (interquartile range, 5.9 to 62.3 BAU / mL) to 145 BAU / mL (interquartile range, 27.6 at 243 BAU / mL) (Figure) and 50% of patients reached the threshold of 143 BAU / mL. Patients who reached this threshold had a longer interval between their transplant and the fourth dose of vaccine and were less frequently treated with steroids (table). The percentage of patients who had anti-peak IgG titers greater than 143 BAU / mL after the fourth dose was 48% for the BNT162b2 vaccine and 52% for the mRNA-1273 vaccine, and patients who received mRNA-1273 vaccine had higher IgG titers (median, 150 vs. 122 BAU / mL). Only one patient was subsequently diagnosed with mild COVID-19, and he had an anti-peak IgG level of 28 BAU / mL 1 month after his fourth dose of the vaccine.
Discussion: Our study indicates that a fourth dose of an mRNA vaccine produces a satisfactory antibody response in some kidney transplant recipients who have not responded adequately after 3 previous doses, and supports the use of ‘a fourth dose of vaccine for these patients. We showed in an unpublished study that kidney transplant recipients with previous COVID-19 had higher antispike IgG titers than uninfected recipients who were vaccinated. Assuming that the difference can be attributed to a higher antigen dose with infection than with vaccination, these results also support the use of additional repeated doses of vaccine for unresponsive kidney transplant recipients. adequately to standard vaccination. Prophylactic infusion of anti-SARS-CoV-2 monoclonal antibodies may be offered to patients who do not respond adequately to additional vaccine doses (5). For example, in our experience, only 10% of patients who did not respond (<1 BAU / mL) after the third dose were able to achieve anti-peak IgG titers greater than 143 BAU / mL after a fourth dose. . It would have been interesting to examine T cell immunity after repeated doses of vaccine in these patients, but the tests are time consuming, making it difficult to perform in routine practice. Finally, we recognize that increased titers of antispike IgG do not invariably offer protection against infection and disease, which is why we encourage longitudinal studies with sufficient follow-up time to assess the risk of COVID- 19 in patients like these after doses of vaccine.
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