Vaccination of solid organ transplant recipients previously infected with SARS-CoV2 induces potent responses that extend to variants, including Omicron

BackgroundMultiple factors affecting COVID19 vaccine induced antibody responses in SARS-CoV2 uninfected immunosuppressed solid organ transplant recipients have been reported; however, there is still a lack of information on non-ACE2 competing cross-CoV2 neutralizing functional antibodies induced in these cohorts, and similarly the vaccine efficacy in prior CoV2-infected immunosuppressed individuals is not well understood. MethodsCOVID19 vaccine efficacy was compared in a panel of kidney and heart transplant recipients who were either CoV2 uninfected (n=63) or CoV2 infected (n=13) prior to receiving two or three doses of mRNA vaccines using pseudoviral neutralization assays against eight CoV2 strains (the CoV2_D614G ancestral strain, alpha, beta, gamma, delta, kappa, lambda, and omicron-BA1 variants), while plasma antibody titers were determined by ELISA using recombinant CoV2-RBD-wt proteins. ResultsMinimally protective neutralizing plasma antibody titers (IC50 [≥] 1:50) against the variants were recorded 7-14% and 25-35% after the second and third doses respectively, with Omicron being the most resistant. In contrast, all previously infected vaccinees possessed minimal protective plasma titers against D614G after either two or three vaccine doses, with 11/13 exhibiting strong protection (IC50[≥] 1:500) and 10/13 exceeding the minimal protective titer against Omicron. Absorption of the selected plasma with immobilized parental RBD removed [≥] 90% of its neutralizing activity, indicating that the dominant neutralization targets were in the RBD. ConclusionsThis study showed that CoV2 infection followed by vaccination, but not vaccination alone, induces the presence of potent highly cross-reactive CoV2 neutralizing plasma antibodies that extend to Omicron variants, even in immunosuppressed SOTRs.