*Purpose: To compare antibody response to a third dose (D3) of SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs) with negative or low-positive antibody levels after 2-dose mRNA vaccination across D3 platforms.

*Methods: From our observational study, 532 SOTRs who developed suboptimal antibody responses to 2-dose mRNA vaccination (Roche<50 U/mL or EUROIMMUN <1.1 AU) were selected. Belatacept recipients and persons with any COVID-19 diagnosis were excluded. We compared post-D3 antibody levels among SOTRs who received an mRNA vaccine for D3 (n=487) versus Ad.26.COV2.S for D3 (n=45). Poisson regression with robust standard error was used to study the association between vaccine platform and seroconversion, adjusting for immunosuppression, age, time since transplant, and liver transplant status.

*Results: Pre-D3, 342 SOTRs (64%) were seronegative, of whom 107 (31%) developed high-positive antibody levels post-D3. In contrast, of the 190 (36%) with low-positive pre-D3 antibody levels, 172 (91%) were high-positive post-D3 (Figure 1). Among SOTRs seronegative pre-D3, 1.8x more Ad.26.COV2.S D3 recipients seroconverted compared to mRNA D3 recipients (49.7% vs 27.8%, Fisher’s exact=0.014) (Figure 2). Among the pre-D3 seronegative group, there was a 2x higher chance of developing high-positive post-D3 levels with Ad.26.COV2.S compared to mRNA D3 (IRR =_1.42.0_2.9, p<0.001). This was despite the Ad.26.COV2.S D3 group having fewer younger patients and liver transplant recipients, factors that are associated with higher odds of positive antibody response. 165 SOTRs (31%) remained seronegative after D3 (22% of Ad.26.COV2.S recipients vs 32% of mRNA recipients).

*Conclusions: Heterologous boosting with Ad.26.COV2.S may be a promising vaccination option for SOTRs with poor response to the 2-dose mRNA series, particularly among those who are seronegative.

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