The global COVID-19 pandemic highlighted the importance of understanding how different populations respond to vaccination, particularly those with compromised immune systems. Vaccines haven’t offered the same protection to those with immunosuppression as they have to the general population. People who have received organ transplants were more likely to have low antibody titers and to experience serious infections following vaccination.

Children have been generally less impacted by COVID-19, but there has been limited assessment of responses to mRNA COVID-19 vaccination in pediatric solid organ transplant recipients (pSOTRs). Our paper highlights distinct immune responses, both antibody- and T cell-mediated, to mRNA COVID-19 vaccination, between pSOTRs and their immunocompetent siblings, shedding light on the path toward optimized vaccination strategies.

Despite immunosuppressive treatments to prevent organ rejection, our study showed that pSOTRs generated antibody responses comparable to healthy children. Following vaccination, both groups had similar levels of antibodies against SARS-CoV-2 and antibodies with neutralizing capacities against both the ancestral strain and the Omicron BA.5 variant. This finding is encouraging, indicating that despite immunosuppression, pSOTRs can achieve protective antibody levels against the virus.

The narrative deepens upon exploring T cell responses, which revealed distinct dynamics between the two groups. Notably, the cytokine profiles elicited by T cells in response to the SARS-CoV-2 spike protein differed significantly in pSOTRs from those observed in healthy children. Cytokines, crucial proteins in immune cell communication, infection response, and inflammation mediation, highlighted this divergence. While T cells from healthy children predominantly produced interferon-gamma, a key player in antiviral defense, pSOTRs exhibited a tendency towards interleukin-2 and tumor necrosis factor production, with a notable reduction in interferon-gamma levels. This distinct pSOTR T cell phenotype raises questions regarding whether it signifies an immunosuppression-induced limitation or an adaptive response potentially conferring protection against the virus.

The introduction of bivalent vaccines, designed to target both the ancestral strain and the Omicron BA.5 variant, was a significant development for immunocompromised groups during the Omicron wave. While it enhanced humoral responses in some pSOTRs in our study two weeks post-vaccination, it did not significantly alter the T cell phenotype of reduced interferon-gamma production. Until we know if the altered T cell responses offer protection, maintaining high titer cross-reactive antibodies through additional vaccine doses is crucial. This strategy could be vital in ensuring adequate protection against subsequent SARS-CoV-2 infections.

Finally, we analyzed the responses of pSOTRs who received three vaccine doses against those of adult SOTRs. The results revealed that children produced stronger antibody and T cell responses, emphasizing that, children with solid organ transplants demonstrate superior immune responses to COVID-19 vaccinations relative to adults. 

The study reveals the resilience and adaptability of the pediatric immune system, even in the face of transplantation and subsequent immunosuppression. However, the qualitatively different T cell responses in pSOTRs raise important questions about the nature of immunity and protection against COVID-19 in this population. This research underscores the need for tailored vaccination strategies for pSOTRs, emphasizing the potential necessity of additional vaccine doses to sustain protective immunity through high titer antibodies given the unclear implications of altered T cell function in protection against severe disease. It also highlights the importance of continuous monitoring and research to understand the long-term implications of these distinct immune responses on vaccine effectiveness and disease outcomes.

As we navigate the evolving landscape of COVID-19, studies like ours provide insights and guidance to healthcare professionals in making evidence-based decisions for some of our most vulnerable populations.

All groups showed similar antibody levels, but distinct T cell responses. Pediatric solid organ transplant recipients’ T cells mainly produce interleukin-2 (IL-2) and tumor necrosis factor (TNF), even after a bivalent dose, without increasing interferon-gamma (IFN-g), crucial for antiviral defense, as seen in healthy children.