Antigen-specific T cell responses following single and co-administration of tick-borne encephalitis, Japanese encephalitis, and yellow fever virus vaccines: Results from an open-label, non-randomized clinical trial-cohort

Abstract

Background Flavivirus infections pose a significant global health burden, highlighting the need for safe and effective vaccination strategies. Co-administration of different vaccines, including licensed flavivirus vaccines, is commonly practiced providing protection against multiple pathogens while also saving time and reducing visits to healthcare units. However, how co-administration of different flavivirus vaccines de facto affects immunogenicity, particu­larly with respect to T cell responses, is only partially understood. Methods and findings Antigen-specific T cell responses were assessed in study participants enrolled in a pre­viously conducted open-label, non-randomized clinical trial. In the trial, vaccines against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), or yellow fever virus (YFV) were administered either individually or concomitantly in different combi­nations in healthy study participants. Peripheral blood samples were collected before vaccination and at multiple time points afterward. To analyze antigen-specific CD4+ and CD8+ T cell responses, PBMCs were stimulated with overlapping peptide pools from TBEV, JEV, YFV, and Zika virus (ZIKV) envelope (E), capsid (C), and non-structural pro­tein 5 (NS5) viral antigens. A flow cytometry-based activation-induced marker (AIM) assay was used to quantify antigen-specific T cell responses. The results revealed remarkably similar frequencies of CD4+ and CD8+ T cell responses, regardless of whether vaccines were administered individually or concomitantly. In addition, administering the vaccines in the same or different upper arms did not markedly affect T cell responses. Finally, limited cross-reactivity was observed between the TBEV, JEV, and YFV vaccines, and related ZIKV-specific antigens. Conclusions TBEV or JEV vaccines can be co-administered with the live attenuated YFV vaccine with­out any markedly altered antigen-specific CD4+ and CD8+ T cell responses to the respec­tive flaviviruses. Additionally, the vaccines can be delivered in the same or different upper arms without any significant altered influence on the T cell response. From a broader per­spective, these results provide valuable insights into the outcome of immune responses fol­lowing simultaneous administration of different vaccines for different but related pathogens.