Despite over four decades of strenuous investigation, a Helicobacter pylori vaccine has not yet been successfully developed, licensed, or implemented in the marketplace. It is important to emphasize that vaccine development for H. pylori has been a public health imperative owing to its plethora of roles in several gastroduodenal pathologies. This unmet challenge has become rather stark in light of its omnipresent worldwide presence, classification as a Group I carcinogen, and ever-growing resistance against antibiotics-mediated eradication therapies (due to rising resistance, treatment failures, and reinfection). In this paper, we propose that the main impediment to the development of an effective vaccine is not the lack of novel antigens for investigation, but rather the lack of adequate understanding of the critical immunopathological requirements for lifelong gastric protection. Supporting this contention, experimental and clinical data suggest that an effective vaccine needs to trigger potent mucosal immunity and antigen-specific cell-mediated responses and generate long-term immunological memory that is capable of subverting H. pylori’s sophisticated immune evasion mechanisms. We review the current paradigms for the use of precision vaccinology, computer-aided antigen identification, immunoinformatics, multi-epitope vaccine strategy, novel adjuvants, delivery vehicles such as nanoparticles and viral vectors, and the newest mRNA platforms to develop H. pylori vaccine candidates. Therefore, these technologies should be viewed as enabling platforms rather than substitutes for a deeper understanding of host–pathogen interactions, gastric mucosal immunity, and the mechanisms required for durable protection. Therefore, future attempts must integrate knowledge from immunology with rational vaccine engineering to produce successful vaccines to prevent and possibly even treat H. pylori infection, thereby limiting the global burden of H. pylori, antimicrobial resistance, and gastric cancer.
La asignación de recursos en la salud pública de España presenta complejos dilemas éticos y económicos, partiendo de la premisa de que las necesidades sanitarias son ilimitadas, mientras que los presupuestos son finitos. En este trabajo se expone la existencia de una asimetría normativa que genera el denominado «sesgo del paciente identificado». Este fenómeno prioriza la medicina asistencial y los fármacos de alto coste para enfermedades raras —impulsados por la compasión social y el «principio de rescate»— frente a una infrautilización estructural de la inversión en medicina preventiva (campañas de vacunación frente a enfermedades inmunoprevenibles); estas, a pesar de su gran beneficio para la seguridad colectiva y su elevado coste-efectividad, afrontan severas trabas de financiación.Para superar esta paradoja y evitar la arbitrariedad política, este documento propone un cambio de paradigma: una reclasificación estructurada en 4 niveles basada estrictamente en la gravedad de la situación clínica y el riesgo vital del individuo, garantizando el derecho al rescate según el sufrimiento y no el diagnóstico. Este modelo se apoya en 5 parámetros objetivos de evaluación (gravedad, incidencia, coste público, disponibilidad de recursos y perjuicio colectivo por coste de oportunidad) para equilibrar de manera justa la protección de los pacientes más vulnerables con la maximización del beneficio de la población.
Glioblastoma (GBM) remains a highly aggressive tumor, characterized by its heterogeneity and profound ability to suppress both innate and adaptive immunity. Dendritic cell (DC) vaccines have emerged as a leading immunotherapeutic strategy to counteract this by restoring effective antigen presentation and generating tumor-specific T-cell responses. This review synthesizes two decades of preclinical and clinical research, outlining the biological rationale and translational progress of DC vaccination for GBM. Preclinical studies have been instrumental, demonstrating that the immunogenicity of the antigen cargo, such as whole tumor lysates, neoantigens, and immunogenic cell death products, critically influences DC activation and subsequent T-cell priming. Parallel advances in DC maturation protocols, including p38 inhibition and α-type-1 skewing, have further enhanced vaccine potency. Clinically, DC vaccines have consistently proven safe and capable of inducing systemic and intratumoral immune activation. Late-phase evaluation of DCVax-L has reported an overall survival advantage in newly diagnosed and recurrent GBM using externally controlled comparisons, although interpretation requires caution because of crossover, endpoint changes, patient heterogeneity, and reliance on matched external controls. However, the efficacy of DC monotherapy is often limited by GBM's immunosuppressive microenvironment, suboptimal DC trafficking, and evolving tumor antigenicity. Consequently, the future of this modality lies in rational combination strategies. Growing evidence supports integrating DC vaccines with immune checkpoint blockade, myeloid-targeted agents, and metabolic modulators to achieve durable tumor control. Coupled with advances in biomarker-driven patient selection and rapid, personalized manufacturing, DC vaccines are paving the way for a new generation of immunotherapy in GBM.
