Background: Infectious diseases remain a major preventable cause of childhood hearing loss. Although the protective effects of certain vaccines, such as those for rubella and meningitis, are well established, a striking paradox exists in global research: over the last 40 years, only nine studies have rigorously evaluated the impact of vaccination on hearing loss. Furthermore, all of these studies originate from high-income countries and cover only three pathogens. This leaves a catastrophic lack of evidence for low- and middle-income countries (LMICs), where approximately 90% of children with hearing loss live. Methods: To address this gap, this narrative review synthesizes evidence primarily drawn from a recent comprehensive scoping review linking 26 vaccine-preventable or potentially preventable deafness-causing infections to 19 vaccines. Rather than repeating established findings, we focus on integrating molecular mechanisms, stratifying direct versus indirect clinical evidence, and translating these insights into an actionable research agenda for LMICs. Results: We also systematically synthesize the molecular mechanisms of pathogen-induced hearing loss, evaluate the direct and indirect clinical evidence, and analyze the recent setback of the 2025 mRNA-1647 Phase III trial to understand the challenges in CMV vaccine development. We propose a targeted, actionable research agenda for LMICs emphasizing the integration of standardized audiological endpoints into future vaccine trials and post-marketing surveillance. Conclusions: The central argument of this review is that the field currently rests on a dangerously thin empirical base. We call for strategic LMIC-led investments and multisectoral collaboration to transform the vast preventive potential of vaccination into tangible global public health benefits.
Dendritic cells (DCs) coordinate antigen presentation and immune-effector activation, but vaccine-induced immune responses have not consistently translated into clinical benefit. This focused narrative review evaluates therapeutic vaccination in established pancreatic cancer and potential adjuvant use after resection, with emphasis on CD34+ progenitor-derived allogeneic DCs engineered to express CD93, CD40 ligand (CD40L), and CXCL13. We develop an integrated framework linking the proposed functions of individual transgenes to donor–recipient–tumor human leukocyte antigen (HLA) compatibility, the strength of the preclinical evidence, and product-specific requirements for translation. Humanized-mouse studies report lymphocyte activation and reduced tumor burden with the complete construct; they do not establish the independent contribution of each transgene. In the advanced-disease experiment, only three animals were included per group, and the late absence of detectable bioluminescence was observed in one surviving treated animal. Tumor-antigen-specific killing has not been conclusively separated from alloreactivity, and CXCL13 expression does not establish functional tertiary lymphoid structures. Clinical studies are compared by cell source, antigen preparation, treatment strategy, and outcome, with RNA vaccines identified separately as contextual comparators. Priorities include controlled component testing, recipient-compatible antigen recognition, reproducible post-thaw potency, and pancreatic-model evaluation of chemotherapy sequencing and conditional checkpoint combinations. These findings support further investigation, while safety and clinical benefit of the three-gene product remain unestablished.
Background/Objectives: Maternal-birth cohort studies are critical epidemiologic tools to assess patterns, breadth, and duration of immunity derived from influenza vaccines, natural infections, and maternal immunologic contributions. Historically, this study design has been important to the development of well-designed pediatric vaccines. We reviewed international influenza maternal-birth cohort studies to discern commonalities and gaps in their approaches to evaluating influenza immune development. Methods: We performed a scoping review of published maternal-birth cohorts studying influenza virus infections and immunity. Principal themes included (a) incidence rates and percentages of acute respiratory and influenza infections, (b) sample collection methods, (c) laboratory methods and diagnostic tests, (d) symptomatology and asymptomatic infections, (e) medically attended infections, (f) maternal and child vaccination status, (g) maternal samples and obstetric history, and (h) reported sources of cohort funding. Results: Nine cohorts met the inclusion criteria and were selected for review. Only two cohorts were conducted in countries classified as lower-middle income, and none were conducted in low-income countries. Syndromic definitions, statistical measures, specimen types, and laboratory techniques differed greatly across these cohorts. Most of these cohorts relied on governmental funding. Conclusions: The resource- and time-intensive information obtained from each of these cohorts independently contributes valuable knowledge to the study of influenza exposures and immunity. However, cross-cohort comparisons and analyses are challenged by methodologic variability. Scientific knowledge could be improved by including cohorts of infants at high risk of negative influenza outcomes, by purposeful standardization of core data element collection, timing, and procedures, by standardized analytic measurements, and by coordinated reporting of results of scientific interest.
Maternal messenger RNA (mRNA) vaccination can generate maternal immunity and antibodies for passive infant protection. However, clinical evidence derives predominantly from the SARS-CoV-2 vaccines BNT162b2 and mRNA-1273, limiting generalization across the platform. This narrative review examines three questions: what determines maternal immune responses, what governs placental antibody transfer, and how immunological findings relate to infant clinical protection. Studies generally support preserved immune responsiveness during pregnancy, but associations with gestational timing are difficult to separate from dose number, previous infection, and time since antigen exposure. Transfer requires interpretation of maternal and cord-blood concentrations, because high transfer ratios do not necessarily indicate high infant antibody levels. Postnatal antibody decline and variant-dependent neutralization further limit inference from measurements at delivery. Observational studies associate maternal vaccination with reduced COVID-19-associated infant hospitalization, although residual confounding and heterogeneous exposure histories complicate comparisons between schedules. No validated infant antibody threshold predicts protection against SARS-CoV-2 infection or hospitalization. Evidence for other pathogens and self-amplifying RNA remains predominantly preclinical. Maternal immunogenicity, placental transfer, and antibody persistence therefore provide complementary evidence but cannot substitute for clinical outcomes. Future products require pregnancy-specific safety assessment and prospective studies linking maternal responses, functional antibody transfer, and postnatal persistence to clinically meaningful protection throughout infancy.
Background: Emerging and re-emerging infectious diseases pose a growing global threat, underscoring the need for vaccine platforms enabling rapid deployment and durable, broad protection. Although mRNA and viral vector vaccines transformed pandemic responses, limitations include waning immunity, restricted antigenic breadth, pre-existing vector immunity, and rare vector-associated adverse events. Here, we evaluate recombinant adenovirus serotypes 4, 28, and 48 expressing a centralized H5 influenza hemagglutinin consensus antigen as next-generation vectors for broad, single-dose protection against diverse H5 influenza clades. Methods: An H5 centralized consensus vaccine was designed using human sequences from the 2003–2006 bird flu outbreak and cloned into four low-prevalence recombinant adenoviruses. Mice received a single intramuscular or intranasal vaccination and were challenged two weeks later with high doses of diverse, lethal, reverse-genetics-derived H5N1 viruses. Immune correlates, survival, and protection from challenge-associated weight loss were assessed. Results: Vaccinated mice were largely protected from lethal challenge against strains spanning twenty years of influenza evolution. Both vaccination routes conferred complete protection against antigenically related strains, and strong protection against more divergent clade 2.3.4.4b strains. Protection occurred before neutralizing antibodies could be detected, although strong H5 antibody responses were induced by all vaccines. Intramuscular vaccination generated strong serum IgG and antigen-specific T cell responses, while intranasal vaccination promoted robust antigen-specific mucosal IgA production. Conclusions: Adenovirus vectors expressing a centralized H5 consensus hemagglutinin elicit rapid, broad protection against diverse H5 influenza viruses following a single intramuscular or intranasal immunization. These results support the continued development of low-seroprevalence adenoviral vectors as a next-generation influenza vaccine platform for rapidly emerging influenza viruses.
