*Purpose: Liver transplant (LT) recipients have a decreased response to 2 doses of SARS-CoV-2 vaccine compared to the general population, so we aimed to understand response to a third dose to inform vaccination strategies.

*Methods: LT recipients in our observational cohort who received 3 homologous mRNA vaccines and available antibody levels pre- and post-dose 3 (D3) were identified. Those who reported a prior COVID-19 diagnosis or used belatacept were excluded. The peak anti-spike antibody level collected between the second (D2) and third dose (D3), was compared to the antibody level at 1 month post-D3. Samples were tested with Roche Elecsys Anti-Sars-CoV-2 enzyme immunoassay (EIA) (positive ≥0.8 U/mL) or EUROIMMUN EIA (positive ≥1.1 AU).

*Results: 146 participants completed 3 homologous doses of BNT162b2 (53%) or mRNA-1273 (47%) vaccines between 5/15/2021 – 11/8/2021. The median (IQR) time of peak pre-D3 antibody collection was 89 (31, 104) days post-D2. The median time of 1-month post-D3 antibody collection was 30 (23, 33) days. The median time between D2 and D3 was 168 (149-188) days. Overall, 125/146 (86%) were seropositive pre-D3, and 139/146 (95%) were seropositive post-D3 (Figure 1). There were no seroreversions post D3, and among the 21 seronegative recipients pre-D3, 14 (67%) seroconverted post-D3. Risk factors significantly associated with persistent seronegativity post-D3 were less time since LT (1.3 vs 6 years, p=0.042), mycophenolate use (100% vs 37%, p=0.001), BNT162b2 series (100% vs 50%, p=0.01), and pre-D3 seronegative status (86% vs 10%, p<0.001).

*Conclusions: Most LT recipients have excellent responses to a third homologous mRNA vaccine dose, greater than that seen in other transplant recipients. Persons seronegative after D2, however, show weaker response and may remain at high risk for SARS-CoV-2 infection despite D3.

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