Beatriz Lazaro-Martin

Background: Vaccination is a key strategy to reduce infectious disease mortality. In pediatric heart transplant recipients (HTRs), the use of immunosuppressive therapy weakens immune responses, increasing the risk of viral infections. This study aimed to evaluate the immunogenicity of hepatitis B virus (HBV) revaccination in this vulnerable population. Methods: A prospective longitudinal study was conducted in HTRs under 18 years of age who received HBV revaccination. Blood samples were collected at study inclusion (baseline) and after the final vaccine dose post-solid organ transplant (SOT; follow-up). Seroprotection was measured by quantifying plasma antibodies to hepatitis B surface antigen (anti-HBs) IgG. Cellular responses were assessed by flow cytometry, evaluating HBV-specific T-cell and natural killer (NK) cell activity following in vitro stimulation with HBV peptides. Results: Twenty-three patients (median age, 9 years; 70% male) were included, with a median posttransplant time of 13 months. All received tacrolimus; most received mycophenolate (87%) and corticosteroids (39%). Post-SOT seroprotection was achieved in 48% of patients, and 82% showed HBV-specific CD4+ and CD8+ T-cell responses. Higher vaccine doses (3–4 doses) were associated with stronger immune responses. NK cell responses were observed in 56% (total NK cells) and 61% (NK T cells). NK responders showed higher expression of the activating receptor NKG2C. Baseline monocyte, dendritic cell and memory T-cell frequencies were positively correlated with post-SOT vaccination response. Conclusions: Pediatric HTRs showed a generally good immune response to HBV revaccination, especially with higher vaccine doses. The immune profile at the time of vaccination appears to influence outcomes, supporting personalized vaccination approaches in immunosuppressed populations.

Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.