(347) Augmented Humoral Response to a Third and Fourth Dose of Mrna Sars-Cov-2 Vaccines in Lung Transplant Recipients

Purpose Lung transplant recipients (LTRs) are at the greatest risk for mortality of COVID-19 among recipients of solid organ transplantation. However, LTRs have been shown to have impaired humoral response (0-40%) to the two doses of mRNA SARS-CoV-2 vaccine. In this study, we aimed to assess the humoral response to a third and fourth dose of SARS-CoV-2 mRNA vaccines in LTRs. Methods This was a prospective observational study of 45 LTRs without a history of SARS-CoV-2 infection, who received two or more doses of the BNT162b2 or mRNA-1273 vaccines between April and October 2022. Among these, 11, 26 and 8 LTRs received 2, 3 and 4 doses of the vaccine, respectively. The levels of antibodies to SARS-CoV-2 spike protein were tested by quantitative immunochromatographic assay. LTRs with antibody titers of 250 AU/mL or higher were defined as responders, which corresponds to two-fold the LD50 concentration level in vitro. Results The median age of the LTRs was 50 years (interquartile range [IQR], 34-59), and 77% of the LTRs were female. The median time from transplantation to anti-SARS-CoV-2 IgG test was 82 months (IQR, 35-124), and the median time from the last dose to anti-SARS-CoV-2 IgG test was 101 days (IGR, 60-158). The maintenance immunosuppression included calcineurin inhibitors (100%), mycophenolate mofetil (95%), and corticosteroids (100%). The humoral responses were detected in 0%, 31%, and 50% of LTRs and the median titers of anti-SARS-CoV-2 IgG were 0.01 AU/ml (IQR, 0.01-0.01), 0.01 AU/ml (IQR, 0.01-335.25), and 1429.48 AU/mL (IQR, 32.06-8195.91) after the second, third and fourth vaccination, respectively. The response rate and the levels of antibodies significantly increased with the numbers of vaccinations (p = 0.027). No patient had acute rejection or serious adverse events within the study period. Conclusion Augmented humoral response was achieved in the LTRs after the third and fourth vaccine dose. Repeated vaccination may be beneficial to enhance humoral immunity even in the LTRs.