(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.