Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).

Background: The primary objective of this work was to assess the prevalence and distribution of HPV genotypes in immunosuppressed patients, and to compare them with the French Monsonego cohort. Secondary objectives were to evaluate whether the risk of HPV infection was correlated with HIV viral load, CD4 cell count in HIV-infected patients and the type, number of immunosuppressive therapies or type of pathology (transplant vs. autoimmune diseases) in patients undergoing long-term immunosuppressive therapy. Methods: An observational, monocentric and historical study was conducted including all immunosuppressed patients having received an HPV testing, in the Laboratory of Virology, Nancy Regional Teaching Hospital Center, between 2014 and 2020. Immunosuppressed patients were either HIV-infected or received long-term immunosuppressive therapy. Results: In our cohort, the prevalence of HPV infection (75.6% vs. 16.1% p < 0.05), the proportion of patients with high-risk HPV infection (48.9% vs. 15.1% p < 0.05) and with multiple HPV infection (41.1% vs. 5.7% p < 0.05) were significantly higher than in the Monsonego cohort. HPV 52 (13%), 53 (13%) and 16 (10%) were the most common in the immunosuppressed population, while it was HPV 16, 42 and 51 in the Monsonego cohort. Conclusions: This study supports that a particular attention must be given to all the immunosuppressed patients for the screening and care of HPV-related diseases because of major modifications of HPV epidemiology compared with the overall population.

BACKGROUND: Enteroviruses (EV)-A71 and EV-D68 are potentially associated with severe clinical conditions, especially in infants and young children. Population susceptibility to these viruses is unknown in France. AIM: We sought to estimate seroprevalence of EV-A71 and EV-D68 neutralising antibodies (nAbs) among children and adolescents living in France. METHODS: A stratified sampling approach based on sex, age and geographical area of residence was applied to obtain sera for routine diagnostic from ˂ 18-year-olds in metropolitan France. A total of 501 serum samples collected between 2023 and 2025 from 0–17-year-olds were included in the investigation. Neutralising activity was tested against EV-A71 sub-genogroup C1 and EV-D68 subclade B3 strains isolated in 2016, allowing to determine seropositivity and nAb titre. Data were analysed overall, by sex, age group and geographical area. RESULTS: For EV-A71, the overall estimated seroprevalence was 43.7% (95% CI: 39.3−48.2) while for EV-D68 this reached 96.0% (95% CI: 93.9–97.5). No differences according to sex were observed. Unlike EV-D68, EV-A71 seropositivity rate varied significantly by age group (p = 0.002) and area of residence (p < 0.001). Notably, 23 of 25 children aged ˂ 1 year lacked EV-A71 protective antibodies. Concerning nAb titres, significant differences occurred across age groups both for EV-A71 (p = 0.004) and EV-D68 (p < 0.001). The nAb titres appeared as highest in 1 to under-2-year-olds for EV-A71 and 0 to under-1-year-olds for EV-D68. CONCLUSION: This seroprevalence study in France reveals a high proportion of newborns and infants susceptible to EV-A71 at potential risk of severe disease, contrasting with the high level of immunity against EV-D68 across all paediatric age groups.