Chronic hepatitis B (CHB) is a global epidemic that can lead to severe liver diseases such as hepatic failure, liver cirrhosis, and hepatocellular carcinoma. Tenofovir alafenamide (TAF), a first-line antiviral drug for CHB, effectively suppresses viral replication but may cause dyslipidemia and alter gut microbiota with long-term use. This study aimed to investigate the effects of a probiotic consortium on the gut-liver axis in TAF-treated CHB patients. In a 12-week randomized double-blind trial, 84 CHB patients receiving TAF monotherapy were assigned to either probiotics (3 × 10¹⁰ CFU/day) or placebo. The primary outcomes were lipid profiles and gut microbiota composition, while secondary outcomes included liver function tests and gastrointestinal symptoms. Results showed that the probiotic group had stable atherogenic lipids compared to placebo. Microbiota analysis revealed specific modulation with increased Parabacteroides (2.1-fold, p = 0.018) and decreased Erysipelotrichaceae_UCG-003 (58

Trauma, disaster, and conflict-related injuries can create clinically important co-exposure to Pseudomonas aeruginosa (PA) and tetanus toxin, where disrupted barriers and contaminated wounds enable simultaneous bacterial infection and toxin entry. Until now no licensed PA vaccine exists and multi-dose schedules are difficult to complete in emergency settings, thus a single-dose, dual-indication vaccine that provides rapid and durable protection is urgently needed. Here, we engineered and characterized a lumazine synthase (LS) nanoparticle vaccine (rePO-TTFC@LS) that co-displays a PA antigen (rePO; PcrV-OprI fusion) and tetanus toxin fragment C (TTFC). In BALB/c mice, rePO-TTFC@LS enhanced antigen uptake and dendritic-cell activation relative to soluble antigens. After a single intramuscular immunization, rePO-TTFC@LS elicited rapid, high anti-rePO and anti-TTFC IgG responses together with increased IFN-γ/IL-4/IL-17A-secreting splenocytes. Vaccination reduced lung bacterial burden and pulmonary IL-1β/IL-6 and improved survival and clinical outcomes in an acute PA pneumonia model, which provided complete protection against lethal tetanus toxin challenge, and decreased PA colonization with improved survival in a femoral fracture-implant co-infection model. Elevated antibody titers and dual protection persisted to 28 weeks after one dose, and biosafety assessments showed no meaningful hemolysis or cytotoxicity and no abnormalities in hematology/serum biochemistry or multiorgan histopathology. Collectively, these results support rePO-TTFC@LS as a single-dose, durable dual-indication nanoparticle vaccine and highlight a modular strategy for combination vaccines suited to mixed-exposure emergency scenarios.

AIMS:To evaluate the association of frailty with mortality and incident extrahepatic diseases in individuals with metabolic dysfunction-associated steatotic liver disease and the interaction between frailty and cardiovascular health. METHODS:This prospective cohort study included 107,867 participants with metabolic dysfunction-associated steatotic liver disease from the UK Biobank. Metabolic dysfunction-associated steatotic liver disease is defined as hepatic steatosis plus cardiometabolic abnormality. Frailty was assessed as physical frailty based on five components (weight loss, exhaustion, physical activity, gait speed, and grip strength) and the Rockwood frailty index, while cardiovascular health was evaluated using the Life's Essential 8 score. RESULTS:Frailty was associated with increased risks of all-cause mortality (physical frailty: HR 2.01, 95% CI 1.87-2.16; frailty index: HR 1.63, 95% CI 1.54-1.74) and incident extrahepatic diseases with the exception of cancer (physical frailty: HRs ranged from 1.62 to 3.35; frailty index: HRs ranged from 1.34 to 8.07). Among the five components of physical frailty, slow gait speed exhibited the strongest associations with most adverse outcomes. There were significant multiplicative and additive interactions between frailty and cardiovascular health on respiratory disease mortality, heart failure, and peripheral arterial disease. Compared with participants with no frailty and good cardiovascular health, those with both frailty and poor cardiovascular health had the highest risks of all adverse outcomes. CONCLUSION:Frailty was associated with increased risks of mortality and extrahepatic complications in metabolic dysfunction-associated steatotic liver disease, particularly in those with suboptimal cardiovascular health. Early detection and interventions for frailty are needed alongside cardiovascular health promotion to enhance the prognosis of metabolic dysfunction-associated steatotic liver disease.

Hepatic steatosis measured by imaging fails to capture the variation in cardiometabolic risk and intervention response, which may be better characterized by metabolomic profiles. We aimed to construct metabolomics-based indices to define this variation. Using data from a three-arm lifestyle intervention randomized trial in adults with type 2 diabetes (T2D) and overweight/obesity, we constructed two novel indices from untargeted plasma metabolomics and MRI-measured liver fat: a metabolomics-based liver fat score (mliver fat), and the discordance between mliver fat and MRI-measured liver fat (Δliver fat). We examined their associations with cardiometabolic traits and intervention response. Both mliver fat and Δliver fat were associated with body composition, glucose indices, insulin sensitivity, and triglyceride, but only Δliver fat was independent of MRI-measured liver fat. Despite having comparable MRI-measured liver fat, compared with the participants with a high Δliver fat (mliver fat > MRI-measured liver fat), those with a low Δliver fat (mliver fat < MRI-measured liver fat) had a more favorable cardiometabolic profile and derived greater benefits and more sustained benefits from diet intervention, with more pronounced long-term improvements in weight, insulin sensitivity, and β-cell function. Among individuals with T2D, a metabolomics-based liver fat score, particularly the discordance between metabolomic and imaging assessments, identifies systemic metabolic heterogeneity and differential responsiveness to lifestyle interventions. Future research is warranted to evaluate its performance in improving risk stratification and personalizing lifestyle intervention. NCT03839667

Background: DNA vaccines are widely used due to their low production cost, ease of large-scale manufacturing, and rapid responsiveness to emerging epidemics. However, their relatively modest immunogenicity in larger species often requires potent adjuvants to elicit robust protective responses. GM-CSF and Flt3L are two cytokine adjuvants targeting dendritic cells (DCs). Although their combination has been reported to augment immune responses, the mechanism underlying the complementary effects of a genetically fused GM-CSF-Flt3L adjuvant plasmid remains incompletely understood. Methods: We constructed a GM-CSF-Flt3L fusion adjuvant plasmid and compared it with single-adjuvant plasmids for their effects on innate, humoral, and cellular immunity, as well as protective efficacy against lethal homologous virus challenge. Results: Compared with single-adjuvant plasmids, GM-CSF-Flt3L synergistically promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and activated draining lymph node DCs, differentially expanded DC subsets, and enhanced the recruitment of migratory DCs. This adjuvant significantly elevated hemagglutinin (HA)-specific serum IgG titers, hemagglutination inhibition (HI) titers, and the responses of T follicular helper (TFH) cells and germinal center B (GCB) cells, while also enhancing the capacity of HA-specific CD4+ and CD8+ T cells to secrete IFN-γ and TNF-α. Following lethal homologous virus challenge, the GM-CSF-Flt3L group exhibited markedly reduced lung viral loads and no significant pathological damage in lung tissues. Conclusions: These findings demonstrate that the GM-CSF-Flt3L fusion adjuvant complementarily enhances humoral and cellular immune responses induced by the influenza DNA vaccine and improves protective efficacy, highlighting its potential as an effective DNA vaccine adjuvant.

Glucagon-like peptide-1 receptor (GLP1R) agonists and dual glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor (GIPR/GLP1R) agonists are established treatments for diabetes and obesity, but their potential effects on biological aging remain uncertain. In this drug target Mendelian randomization study, we assessed the associations of genetically proxied modulation of GLP1R, GIPR, and dual GIPR/GLP1R pathways with four aging phenotypes, including frailty index, phenotypic age (PhenoAge) acceleration, telomere length, and longevity. Glycated hemoglobin (HbA1c) lowering via GIPR, modeling the glucose-lowering effect of variants in GIPR loci, was consistently associated with a lower frailty index (primary dataset: β = − 0.10 [95

Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine performance. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA analog, activates TLR3/RLR pathways to enhance T-cell priming and cellular immunity. However, its utility as a sole adjuvant is limited by rapid nuclease degradation and poor cytosolic delivery. Lipid nanoparticles (LNPs), a mature delivery platform, enable high encapsulation efficiency, efficient cellular uptake, and endosomal escape. Objectives: This study aimed to evaluate the adjuvant effect of LNP-encapsulated PolyI:C (LNP-PolyI:C) on the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. Methods: The colloidal stability of LNP-PolyI:C stored at 2–8 °C for 9 months was monitored using dynamic light scattering (DLS) on a Zetasizer Lab instrument. Serum levels of HBsAg-specific IgG, IgG1, and IgG2a antibodies in immunized Kunming mice were measured by enzyme-linked immunosorbent assay (ELISA). The secretion of HBsAg-specific cytokines by splenocytes was analyzed using flow cytometry and enzyme-linked immunospot (ELISpot) assay. Results: The results demonstrated that the LNP-encapsulated PolyI:C adjuvant significantly increased the secretion of HBsAg-specific IFN-γ, IL-2, and TNF-α by splenocytes, indicating a Th1-biased and cytotoxic T lymphocyte (CTL)-mediated cellular immune response. In addition, this formulation markedly elevated serum titers of HBsAg-specific IgG, IgG1, and IgG2a. Conclusions: These findings underscore the advantages of the LNP-PolyI:C adjuvant in enhancing both humoral and cellular immunity, demonstrating its considerable potential as a novel adjuvant.

On 11–14 March 2026, the Vaccine Innovation Forum World 2026 (VIF World 2026) was held in Shanghai, China.

Exploring the association of clonal haematopoiesis of indeterminate potential (CHIP) with psychiatric disorders (PDs) may help to elucidate the biological mechanisms underlying PDs. The study aimed to identify the specific PD subtypes associated with CHIP and gene-specific CHIP for each PD subtype. A total of 360,451 participants from UK Biobank without PDs at baseline, aged 40–69 years and recruited between 2005 and 2014, were included. CHIP status was determined from whole exome sequencing for mutations in 74 driver genes. Any CHIP (variant allele fraction (VAF) ≥ 2

ABSTRACT Chronic hepatitis B (CHB) remains incurable due to the immune system's tolerance toward the hepatitis B virus (HBV) surface antigen (HBsAg). This study aimed to achieve a functional cure by breaking HBV tolerance through immunotherapy. CHB patients were treated with either standard nucleotide analog (NA) therapy (Adefovir Dipivoxil, ADV) (Cohort 1) or ADV combined with interferon‐alpha (IFN‐α) (Cohort 2). Additionally, a third cohort received the THRIL‐GM‐Vac regimen: three low‐dose GM‐CSF injections followed by one dose of the HBV vaccine, alongside standard treatment. THRIL‐GM‐Vac treatment (Cohort 3) achieved a significant 2log10 reduction in HBsAg levels in 21.7% of participants, and 8.7% HBsAg clearance in Cohort 3 compared to 0% and 4.17% in Cohorts 1 and 2, respectively. Furthermore, THRIL‐GM‐Vac significantly reduced HBV‐specific tolerogenic T cells (Tregs), explaining the sustained HBsAg decrease. Upregulation of anti‐HBV T cell responses confirmed THRIL‐GM‐Vac's ability to disrupt HBV tolerance and enhance HBsAg‐specific cellular immunity. This suggests its potential effectiveness in treating individuals with moderate to low HBsAg levels. THRIL‐GM‐Vac treatment in Cohort 3 resulted in 8.7% HBsAg clearance alongside Treg depletion and enhanced anti‐viral T cell responses. These findings present a promising strategy to overcome immunotolerance and potentially combat chronic HBV infection.

Clonal haematopoiesis of indeterminate potential (CHIP) and low vitamin D are recognised as independent risk factors for type 2 diabetes mellitus (T2DM); however, their joint effects on T2DM incidence remain unclear. We hypothesised that CHIP mutations and vitamin D deficiency may be jointly associated with the risk of T2DM. This study included 405,095 participants from the UK Biobank without T2DM at baseline. CHIP was identified through whole-exome sequencing of peripheral blood samples, and vitamin D was categorised into quartiles. All the participants' variables were tested at baseline. Cox regression was used to evaluate the joint effects of CHIP and vitamin D on incident T2DM. The mean age of the participants was 56.4 ± 8.1 years, and 54.0% were female. After a median follow-up of 12.9 years, 24,724 (6.1%) participants developed T2DM. Multivariable analyses revealed that higher vitamin D quartiles were associated with a lower risk of incident T2DM (HR [95% CI]: 0.89 [0.86-0.92], 0.78 [0.75-0.81], and 0.70 [0.67-0.73] for the 2nd, 3rd, and 4th quartiles vs. Q1, respectively), with similar associations observed in participants with and without CHIP, and no evidence of interaction. In contrast, the presence of CHIP was not clearly associated with incident T2DM after adjustment (HR 1.03 [0.97-1.09]). These findings suggest that vitamin D is associated with type 2 diabetes risk, independent of clonal haematopoiesis, and may help to contextualise risk heterogeneity among individuals with and without CHIP.

In situ vaccination (ISV) triggers antitumor immune responses using the patient’s own cancer antigens, yet limited neoantigen release hampers its efficacy. Our novel combination therapy involves low-dose local cisplatin followed by ISV with a TLR7/8/9 agonist formulation (CR108), in which CR108 boosts and sustains the antitumor responses induced by the cisplatin-released neoantigens. In mouse models, the cisplatin+CR108 combination significantly outperformed cisplatin or CR108 alone in abrogating established 4T1 and B16 tumors. The synergistic antitumor effects of cisplatin and CR108 were accompanied by markedly increased tumor tertiary lymphatic structures (TLS) formation, higher levels of type I and III interferons and TNF-α in serum, augmented T and B lymphocyte infiltration, antigen-presenting cell activation, as well as reduced functionally of exhausted T cells. Single-cell sequencing analysis uncovered a potential pathway for TLS to serve as a reservoir for functional antitumor effector T cells. Furthermore, cisplatin+CR108 combo therapy, but neither cisplatin nor CR108 alone, effectively inhibited the growth of treated 4T-1 tumor in an effector T cell-dependent manner. Notably, the combo therapy also suppressed the growth of distant untreated 4T-1 tumors, demonstrating systemic antitumor effects. Moreover, combo-therapy led to full regression of 4T-1 tumors in a large percentage of mice, who became strongly resistant to secondary tumor challenge, a clear indication of antitumor immunological memory. The cisplatin+CR108 combo therapy holds promise in converting “cold” tumors into “hot” ones and eliciting robust antitumor immune responses in vivo.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder and a major global health challenge, yet effective pharmacological therapies are lacking. Empagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor, has shown systemic metabolic and anti-inflammatory benefits, but its liver-specific molecular mechanisms remain incompletely understood. In this study, we evaluated the therapeutic effects of empagliflozin in a diet-induced mouse model of NAFLD, supported by Mendelian randomization analysis. Histological examination, serum biochemistry, and hepatic triglyceride quantification demonstrated that empagliflozin markedly attenuated hepatic steatosis and improved liver injury indices. At the molecular level, empagliflozin suppressed NF-κB-mediated inflammatory signaling and significantly downregulated fibrotic markers including α-SMA and COL1A1, while modulating TIMP-1 and MMP-9 expression. Collectively, these findings reveal that empagliflozin ameliorates NAFLD by inhibiting inflammatory and fibrotic molecular pathways, highlighting its potential as a mechanism-based therapeutic option for NAFLD.

Traditional DNA vaccines, typically administered via intramuscular injection with electroporation (IM-E), often cause discomfort and require trained personnel. Addressing these challenges, we developed multivalent DNA vaccines targeting both intracellular mature virion (IMV) and extracellular enveloped virion (EEV) proteins of the monkeypox virus (MPXV), designated as M2 (A29L, B6R), M3 (A29L, B6R, M1R) and M4 (A29L, B6R, M1R, A35R). These vaccine constructs were formulated into dissolvable microneedle array patches (D-MAPs) for intradermal delivery. Comparative studies in mice demonstrated that D-MAPs achieved approximately 70% delivery efficiency and elicited robust humoral immune responses in mice, including antigen-specific IgG and cross-neutralising antibodies against MPXV, VACV and ECTV-comparable to those induced by IM-E. Furthermore, D-MAP immunisation induced stronger T cell responses, particularly in the draining lymph nodes. Importantly, the multivalent DNA vaccines-especially M3 and M4-conferred substantial protection against lethal VACV-WR challenge, achieving levels of protection comparable to the traditional replication-competent smallpox vaccine TianTan (VTT), with significant viral suppression and mitigation of pathological damage. Collectively, this study provided valuable insights for the development of innovative MPXV DNA vaccines, highlighting a minimally invasive and suitable for field application with D-MAP with broad potential for combating mpox outbreaks and future orthopoxvirus pandemics.

Background: The blood proteome is a major source of biomarkers and therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify cardiometabolic protein markers for diabetic kidney disease (DKD). Methods: We measured all 369 proteins in the Olink Explore 384 Cardiometabolic and Cardiometabolic panel of 500 patients with type 2 diabetes from 11 communities in Shanghai. Protein quantitative trait loci (pQTLs) were derived by coupling genomic and proteomic data. Cis-pQTLs identified for proteins were used as instrumental variables in MR analyses of DKD risk, and the outcome data were obtained from 8401 Japanese individuals with type 2 diabetes (2809 cases and 5592 controls). Replication MR analysis was performed in the UK Biobank Pharma Proteomics Project (UKB-PPP). Colocalization analysis and the Heidi test were used to examine whether the identified proteins and DKD shared causal variants. Results: Among the 369 proteins, we identified 66 independent cis-pQTLs for 64 proteins. MR analysis suggested that two cardiometabolic proteins (UMOD and SIRPA) may play a causal role in increasing DKD risk, with UMOD showing replication in UKB-PPP. Bayesian colocalization further supported the causal effects of these proteins. Additional analyses indicated that UMOD is highly expressed in renal macrophages. Further downstream analyses suggested that UMOD could be a potential novel target and that SIRPA could be a potential repurposing target for DKD; however, further validation is needed. Conclusions: By integrating proteomic and genetic data from patients with type 2 diabetes, we identified two protein biomarkers potentially associated with DKD risk. These findings provide insights into DKD pathophysiology and therapeutic target development, but further replication and functional studies are needed to confirm these associations.

Background: pGX9501 is a prophylactic DNA vaccine encoding the spike protein of SARS-CoV-2 and can induce immune response in the human body so as to prevent COVID-19. With respect to non-clinical studies, pGX9501 has been demonstrated to induce both cellular and humoral immune responses in various animal models. It was found that the level of antibody titers following a two-dose regimen was higher than that following a single-dose regimen in nonhuman primate challenge model. Methods: In China, a phase I, randomized, double-blind, placebo-controlled clinical trial has been conducted in Huashan Hospital, Shanghai, China to evaluate the safety, tolerability, and immunogenicity of DNA vaccine pGX9501 administered intradermally (ID) followed by electroporation (EP) in 45 Chinese healthy volunteers aged 18 to 59 years old. Results: No adverse events of special interest (AESIs), death, or treatment-related SAEs occurred in this study. All the treatment-related (vaccine or EP) adverse events (TRAEs) were of grade 1 and 2 in severity. The solicited AEs were reported in thirty-two (32/36, 88.9%) and nine (9/9, 100.0%) subjects, respectively, in the DNA vaccine and placebo group. The frequency of solicited AEs did not increase with vaccine dose level and frequency. The DNA vaccine pGX9501 effectively enhanced both humoral and cellular immune responses in a dose-dependent manner, with increased antibody GMTs and peak seroconversion rates observed on day 42. The significant rise in IFN-γ levels confirmed the vaccine’s ability to induce cellular immune responses. Variations in the microbiome structure suggested a tangible impact of the gut microbiota on vaccine immunogenicity. Conclusions: The findings from this study confirm the immunogenicity and safety of the DNA vaccine pGX9501 and point to the potential role of the gut microbiota in vaccine immune responses. These insights provide practical references for the future design and development of DNA vaccines.

OBJECTIVES:We aimed to investigate the association of the status of iodized salt in terms of consumption of salt type and urinary iodine concentration (UIC) in diabetes, with frailty and examine whether this association could be modified by thyroid function. DESIGN:A population-based cohort study. SETTING AND PARTICIPANTS:We included 850 patients with type 2 diabetes from 11 communities in Shanghai, who completed five-year follow-up. MEASUREMENTS:The type of salt consumed was collected through a standardized questionnaire and UIC was measured by an inductively coupled plasma-mass spectrometer. Frailty was assessed by frailty phenotype. Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured by electrochemiluminescence. Modified Poisson regression model with robust variance was used to estimate the relative risks (RRs) with 95% confidence intervals (CIs) for frailty in relation to iodized salt consumption and UIC. RESULTS:In this five-year follow-up study in patients with diabetes, 111 (12.9%) patients progressed to frailty. Patients who consumed non-iodized salt (RR: 1.09, 95% CI: 1.01-1.18) had an increased risk of frailty, compared to patients who consumed iodized salt. Lower UIC was associated with a higher risk of frailty (1.10, 1.01-1.19). In patients with high TSH and low FT4, the RRs of frailty were 1.20 (1.08-1.34) and 1.15 (1.02-1.29) for non-iodized salt, and 1.14 (1.02-1.28) and 1.12 (0.99-1.27) for low UIC. CONCLUSIONS:Non-iodized salt consumed and low UIC were associated with an increased risk of frailty in diabetes, particularly in those with high TSH and low FT4. Maintaining adequate iodine intake is critically important for preventing frailty in diabetes, especially for individuals with potential thyroid dysfunction.

Background: Much remains unknown about the associations between adverse childhood experiences (ACEs), adverse adulthood experiences (AAEs) and the risk of neurodegenerative diseases, including dementia and Parkinson's disease (PD).Purpose: To examine the associations of ACEs and AAEs with incident dementia and PD, and to evaluate their interactions with genetic risk.Methods: We included 147,942 participants (mean [SD]: 55.9 [7.7] years) without dementia and PD at baseline from UK Biobank. ACEs and AAEs were assessed through an online mental health questionnaire, including emotional neglect, physical abuse, emotional abuse, sexual abuse, and physical neglect. Polygenic risk scores (PRS) were constructed for dementia and PD. Replication analysis was conducted in the China Health and Retirement Longitudinal Study (CHARLS) cohort.Results: During a median follow-up of 15.1 years, 851 incident dementia and 729 PD cases occurred. A greater number of ACEs was associated with increased risks of dementia (HR, 1.14, 95% CI: 1.08-1.21, per additional ACE) and PD (1.11, 1.04-1.18). Similarly, a higher number of AAEs was linked to elevated risks of dementia (1.16, 1.09-1.24) and PD (1.02, 0.95-1.10), though the latter was not statistically significant. Moreover, significant additive interactions between ACEs, AAEs, and genetic risk were observed for dementia, which accounted for an additional 13% to 19% of dementia cases. Results from the CHARLS confirmed the associations of ACEs and AAEs with dementia and PD.Conclusions: Exposure to ACEs or AAEs was associated with increased risks of dementia and PD. The dementia risk associated with ACEs was amplified in individuals with AAEs or high genetic susceptibility. These findings highlight the importance of life-course prevention targeting both ACEs and AAEs in mitigating dementia and PD risks, particularly among individuals with high genetic susceptibility. These findings should be interpreted with caution due to potential recall bias, self-reported assessments, and selection bias.

Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria. Nasal or oral administration has the advantage of being needle free and self-administered, thereby improving compliance and coverage of large populations. In China, the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy. The hurdles we are facing in the development of mucosal vaccines, however, come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines. Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration, not only at the scientific level but, most importantly, by engaging public and private health organizations, governments, and regulatory authorities. We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.