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BACKGROUND: Immunosuppressive therapy following solid organ transplantation inhibits protective immunity to pathogens and vaccines. However, the specific cell states associated with failure to generate responsiveness to vaccination are not known.METHODS: We evaluated a broad spectrum of immune cell states within peripheral blood of twelve pediatric solid organ transplant recipients (SOTR) and eight healthy children immediately prior to receiving SARS-CoV-2 vaccination, by performing single cell RNA-sequencing, T cell receptor sequencing and Cytometry by Time-Of-Flight. We then evaluated associations between the identified cell states and the development of anti-SARS-CoV-2 S-protein specific antibody and CD4+ T cell activation following an initial series of SARS-CoV-2 vaccinations.RESULTS: We found clonal expansion of a subset of CD8+ effector T cells and a polyclonal expansion of CD4+ effector T cell populations in SOTR compared to healthy controls. Responses to vaccination included normal SARS-CoV-2 specific T cell and antibody responses, intact T cell but impaired antibody responses, and absence of T cell and antibody responses. Comparison among the pre-vaccination cell states and responsiveness revealed a higher frequency of atypical B cells in SOTR with intact T cell, but impaired antibody responses compared to healthy controls. Also, T cell only SOTR responders had lower numbers of immature γδ T cells compared to SOTR non-responders. In contrast, there was no definitive cell state that identified an absent immune response in SOTR, but interactome analysis suggested that robust cellular interactions between myeloid, T cells and B cells are required for successful responses to vaccination.CONCLUSIONS: Our findings in this exploratory observational study suggest that higher frequencies of atypical B cells in the peripheral blood of pediatric SOTR may identify intact cellular but absent humoral responsiveness to vaccination. Intact T cell responsiveness to antigen may be sufficient to monitor protective immunity following vaccination in SOTR.