Vaccines最新文献

{"title":"Stepwise Evolution of Immunodeficient Mouse Models: Focus on NCG Strains and Their Applications in Humanized Immune System Research.","authors":"Hongyan Sun, Jialu Fan, Yujing Zhang, Jun Xing, Yinlian Zhang, Cunxiang Ju, Juan Liang","doi":"10.3390/vaccines14090805","DOIUrl":"10.3390/vaccines14090805","url":null,"abstract":"<p><p>Immunodeficient and humanized mouse models have become essential tools for investigating human immunity, disease pathogenesis, and therapeutic evaluation. This review summarizes the stepwise evolution of these platforms, from nude and SCID mice to advanced NOD/SCID/<i>Il2rg^null</i> strains (NCG, NSG, or NOG), and highlights how progressive removal of murine immune barriers has improved human cell engraftment and experimental utility. Major humanized immune system (HIS) approaches, including Hu-PBMC/PBL, Hu-HSC, and Hu-BLT models, are compared with respect to engraftment kinetics, immune composition, graft-versus-host disease, and suitability for distinct research applications. Particular emphasis is placed on next-generation engineered strains that enhance specific human immune compartments, including cytokine-humanized models for myeloid, dendritic cell, natural killer cell, and neutrophil reconstitution; TSLP-based models that restore secondary lymphoid organogenesis and improve adaptive immune responses; and advanced HLA-humanized models. These advances have substantially expanded the value of humanized mice in studies of autoimmune disease, cancer immunotherapy, and vaccine evaluation. Nevertheless, no single model fully reproduces the complexity of the human immune system, and major limitations remain, including incomplete stromal humanization, restricted HLA diversity, and inter-model variability. Continued refinement will be critical for improving translational relevance and predictive power in vaccine and immunology research.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Public Health Lessons from a Point-Source Polymicrobial Foodborne Outbreak: Implications for Vaccination of Vulnerable Populations.","authors":"Caterina Elisabetta Rizzo, Davide Anzà, Cristina Genovese, Dalila Sciacca, Salvatore Scondotto, Antonio Cristaldi, Vincenzo Restivo","doi":"10.3390/vaccines14090804","DOIUrl":"10.3390/vaccines14090804","url":null,"abstract":"<p><strong>Background: </strong>Foodborne outbreaks remain a major public health concern, particularly for immunocompromised individuals who experience a disproportionate burden of severe enteric disease. Although environmental prevention represents the cornerstone of food safety, outbreak investigations may also provide valuable evidence for identifying populations that could benefit most from future vaccination strategies. This study investigated a point-source foodborne outbreak in Southern Italy to describe clinical outcomes among exposed individuals, including an immunocompromised oncology patient, and to explore the potential relevance of host vulnerability for future enteric vaccine research.</p><p><strong>Methods: </strong>A retrospective cohort study combined with an environmental outbreak investigation was conducted following a restaurant-associated gastroenteritis cluster. Clinical data, epidemiological information, and laboratory findings were collected for all exposed individuals. Stool samples were analyzed using multiplex real-time polymerase chain reaction (RT-PCR), while microbiological and molecular analyses were performed on kitchen water samples collected during the official sanitary inspection.</p><p><strong>Results: </strong>Four of six exposed individuals developed acute gastroenteritis (overall attack rate: 66.7%; food-specific attack rate: 100%) within 24-48 h after consuming the same meal. Three previously healthy adults experienced prolonged symptoms lasting 15-21 days and subsequently developed post-infectious irritable bowel syndrome (PI-IBS) during follow-up. In contrast, a 43-year-old woman receiving cisplatin chemotherapy for cervical cancer developed severe dehydration requiring emergency hospitalization. Multiplex RT-PCR identified polymicrobial infection with <i>Campylobacter</i> spp., norovirus, and three diarrheagenic <i>Escherichia coli</i> pathotypes (EAEC, EPEC, and ETEC). Environmental investigation demonstrated contamination of the restaurant's kitchen water supply with total coliforms (>80 CFU/100 mL), intestinal <i>Enterococci</i> (30 CFU/100 mL) and norovirus genogroups I and II, confirming the common source of exposure.</p><p><strong>Conclusions: </strong>This outbreak demonstrates how identical environmental exposure may result in markedly different clinical outcomes according to host immune status. While rigorous food safety measures remain essential, these findings may help develop hypotheses regarding populations that could be considered in future studies of enteric vaccination strategies. Outbreak investigations may therefore contribute not only to source identification and outbreak control but also to informing future vaccination strategies for vulnerable populations.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Healthcare Professionals' Characteristics and ZIP-Code-Level Income of Their Practice Location with Routine Assessment of HPV Vaccination Status.","authors":"Olajumoke Ope Oladoyin, Paula M Cuccaro, Lara S Savas, Robert Yu, Sheryl McCurdy, Monalisa Chandra, Joel Fokom Domgue, Sanjay Shete","doi":"10.3390/vaccines14090801","DOIUrl":"10.3390/vaccines14090801","url":null,"abstract":"<p><strong>Background: </strong>Although the human papillomavirus (HPV) vaccine has the potential to prevent most HPV-related cancers, its uptake in Texas remains lower than the national uptake and the Healthy People 2030's goal of 80% completion among adolescents. The Centers for Disease Control and Prevention (CDC) advises healthcare professionals (HCPs) to assess immunization status at every clinical encounter and to routinely integrate these standards into their practice. Socioeconomic characteristics of individuals influence HPV vaccination; however, the role of HCPs' individual characteristics and the ZIP-code-level income of their practice location in the routine assessment of HPV vaccination is unknown.</p><p><strong>Methods: </strong>Using data from a survey of HCPs conducted by MD Anderson in Texas in the year 2021, we examined the association between HCPs' individual characteristics and the ZIP-code-level income of their practice location in HCPs' routine assessment of HPV vaccination.</p><p><strong>Results: </strong>This study included 1283 HCPs working in Texas. Overall, 37.6% of HCPs reported routinely assessing HPV vaccination status. Compared with HCPs whose practice was based in lower-income communities (median household income below $56,500), those who practiced in higher-income communities had 32% lower odds of routinely assessing HPV vaccination status (aOR: 0.68; 95% CI: 0.48-0.96). Compared to HCPs without prior formal training on HPV vaccination, the odds of HCPs assessing HPV vaccination status routinely were 393% higher (aOR: 4.93; 95% CI: 3.21-7.58) among HCPs who had formally trained less than two years ago, 123% higher (aOR: 2.23; 95% CI: 1.52-3.28) among HCPs formally trained between two and five years ago, and 92% (aOR: 1.92; 95% CI: 1.28-2.87) higher among HCPs formally trained more than five years ago.</p><p><strong>Conclusions: </strong>Our findings underscore the need for targeted interventions and education to promote routine HPV vaccination communication and status assessment among HCPs in higher-income communities in Texas. These efforts should include approaches to address vaccine hesitancy and introduce reminders and system-level prompts. Future research should investigate the contextual and organizational factors that contribute to these income-related differences to better inform implementation strategies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuity of Vaccination Across the Life Course: Poland in Comparison with Selected EU/EEA Countries and the United Kingdom.","authors":"Ewa Benedyk-Lorens, Maria Leśniak, Olga Lorens, Jadwiga Wójkowska-Mach","doi":"10.3390/vaccines14090802","DOIUrl":"10.3390/vaccines14090802","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Vaccination represents one of the most significant achievements of modern medicine and public health. However, the scope, mandatory status, and vaccination coverage vary considerably across European countries. <b>Methods:</b> This narrative review compares selected elements of vaccination programmes in Poland, purposively selected EU/EEA countries, and the United Kingdom. Official data from the WHO, UNICEF, ECDC, EMA, and national sources were used to delineate vaccination policies, reimbursement models, delivery arrangements, coverage rates, and educational approaches. Due to temporal and methodological heterogeneity, the findings were interpreted descriptively. <b>Results:</b> Poland, together with Latvia, has the largest number of vaccinations classified as mandatory among the EU/EEA countries included in this comparison. Vaccination is mandatory in only nine EU/EEA countries; however, several countries without such policies also report high vaccination coverage in settings characterized by extensive public education and accessible vaccination services. Adult vaccination policies, recommendations, and reimbursement frameworks for influenza, pneumococcal, and RSV vaccines vary significantly depending on the country, target population, age criteria, and scope of funding. <b>Conclusions:</b> This comparison indicates a potential gap between the structured delivery of childhood vaccinations and the predominantly recommendation-based adult vaccination approach in Poland. Strategies utilized in selected European countries suggest that life-course vaccination continuity can be enhanced through accessible delivery systems, adequate reimbursement, systematic assessment of vaccination status, active engagement of healthcare professionals, sustained public communication, and trust-building. Mandatory status alone should not be regarded as sufficient to ensure high vaccination coverage.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration of the Humoral Immune Response to Influenza Vaccination in a Cohort of Repeatedly Vaccinated Adults over Four Consecutive Epidemic Seasons: 2018/19-2021/22 Observational Study.","authors":"Mariia V Sergeeva, Polina Kudar, Yulia Desheva, Ekaterina Romanovskaya-Romanko, Vera Krivitskaya, Janna Buzitskaya, Marina A Stukova, Irina Kiseleva, Dmitry Lioznov","doi":"10.3390/vaccines14090800","DOIUrl":"10.3390/vaccines14090800","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The impact of repeated annual influenza vaccination on long-term immunogenicity and protection remains debated. Although reduced fold-increases in antibody titers are often observed in repeatedly vaccinated individuals, the effect on the duration of the humoral response remains poorly understood. This study evaluated the magnitude and persistence of the humoral immune response over four consecutive seasons. <b>Methods</b>: An open-label observational study was conducted between 2018 and 2022 and involved 28 healthy adults (median age, 55 years) immunized with seasonal inactivated influenza vaccines. Hemagglutination inhibition (HAI) titers were assessed at five time points annually. Secondary endpoints included neutralizing (MNA) and neuraminidase-inhibiting (ELLA) antibody responses measured at baseline and three weeks after vaccination. The duration of antibody responses above the seroprotection threshold (titer ≥ 40) was compared across seasons using the Mantel-Cox test. <b>Results</b>: Antibody dynamics differed by vaccine component. The highest GMT and fold-increase were observed for A/H1N1pdm09 in 2018/19, followed by a significant decline after the second vaccination, that was more pronounced for neutralizing antibodies. The response to N1 neuraminidase remained weak throughout the study. For A/H3N2, baseline HAI GMTs increased significantly after each subsequent vaccination, whereas N2 neuraminidase responses peaked after the first dose and declined thereafter. Influenza B responses were weaker than those to influenza A. A significant increase in B/Yamagata titers in 2020/21 was attributed to the introduction of quadrivalent vaccines. A/H1N1pdm09 HAI responses were long-lasting, with titers remaining at or above the seroprotection threshold for one year. The duration of the A/H3N2 antibody response increased significantly over four seasons, likely because of annual strain updates. A similar trend was observed for B/Victoria after strain changes. <b>Conclusions</b>: Repeated annual influenza vaccination did not negatively affect post-vaccination antibody titers to the HA vaccine antigens in the studied cohort. Regular updates to vaccine strains may enhance the persistence of HA-targeted humoral immune responses.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Intramuscular and Intradermal Porcilis Lawsonia^® Administration Under a Laboratory Challenge Model and Korean Field Conditions.","authors":"Sungseok Lee, Jincheol Kim, Sohyun Seok, Sangwon Lee, Sunsook Hwang, Jinyoung Hwang, Leonardo Domingo Ellerma, Chang-Seon Song","doi":"10.3390/vaccines14090803","DOIUrl":"10.3390/vaccines14090803","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Lawsonia intracellularis</i> is a major enteric pathogen of swine that causes proliferative enteropathy, reduced growth performance, and economic losses. Although vaccination is an effective control strategy, comparative data on the efficacy of intramuscular (IM) and intradermal (ID) administration of inactivated <i>L. intracellularis</i> vaccines are limited. This study evaluated and compared the efficacy of Porcilis Lawsonia^® administered by IM or ID routes under experimental challenge and Korean field conditions. <b>Methods</b>: In a laboratory challenge study, 24 <i>L. intracellularis</i>-negative piglets were assigned to IM-vaccinated, ID-vaccinated, or unvaccinated control groups (<i>n</i> = 8/group). Vaccinated pigs received Porcilis Lawsonia^® and were orally challenged with <i>L. intracellularis</i> four weeks later. Clinical signs, average daily gain (ADG), antibody responses, bacterial shedding, and intestinal lesions were evaluated. In a field trial, 90 piglets from three commercial Korean farms were allocated to IM, ID, or control groups (n = 30/group) and monitored for growth performance, serological responses, and fecal shedding. <b>Results</b>: Under challenge conditions, both IM and ID vaccination significantly reduced clinical signs and fecal shedding while improving ADG and final body weight compared with controls. Vaccinated pigs developed significantly higher antibody responses before challenge. In field trials, both vaccination routes significantly increased body weight at 19 weeks of age and markedly reduced <i>L. intracellularis</i> shedding. No vaccine-related adverse effects were observed. Differences between IM and ID vaccination were generally not significant, although IM vaccination induced slightly higher antibody responses at 13 weeks of age under field conditions. <b>Conclusions</b>: Porcilis Lawsonia^® administered by either IM or ID routes provided comparable protective efficacy against <i>L. intracellularis</i> infection, reducing bacterial shedding and improving growth performance under both experimental and field conditions. These findings support ID vaccination as an effective alternative to conventional IM administration.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine-Associated Enhanced Respiratory Disease: From Animal Models to Human Health.","authors":"Jacob A Dillard, Reina A Saldivar, Mark T Heise, Victoria K Baxter","doi":"10.3390/vaccines14090799","DOIUrl":"10.3390/vaccines14090799","url":null,"abstract":"<p><p>Vaccines are a safe and highly effective tool for protecting both humans and animals against infectious diseases. Although vaccines currently in use in humans have robust safety records, historical examples show that some vaccines have resulted in adverse outcomes, including vaccine-associated enhanced respiratory disease (VAERD). VAERD occurs when preexisting vaccine-induced immunity worsens respiratory disease, rather than conferring protection during infection. Enhanced disease in the lower respiratory tract characteristic of VAERD includes worsened clinical manifestations such as pneumonia and bronchiolitis, as well as increased pulmonary pathology in vaccinated, infected individuals compared with their unvaccinated, infected counterparts. Mechanistically, VAERD has been associated with T_H2-mediated immunopathology or antibody-dependent enhancement and is primarily associated with specific virus families, including <i>Pneumoviridae</i>, <i>Orthomyxoviridae</i> and <i>Coronaviridae</i>. Notable cases of VAERD have been associated with a respiratory syncytial virus vaccine candidate evaluated in clinical trials in the 1960s, experimental coronavirus vaccines in animal models, and in veterinary vaccines for influenza virus in swine. Existing approved vaccines are safe and highly effective tools for protecting both humans and animals against respiratory pathogens. However, as new respiratory vaccines are developed, they must also undergo careful testing for VAERD or other adverse outcomes. This review aims to provide the field with an overview of VAERD as a resource to support vaccine development and safety studies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Vaccines Against Infectious Diseases.","authors":"Salvatore Giovanni De-Simone","doi":"10.3390/vaccines14090796","DOIUrl":"10.3390/vaccines14090796","url":null,"abstract":"<p><p>Vaccination remains one of the most successful interventions in medical history [...].</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evaluation of Novel Conserved <i>Neisseria gonorrhoeae</i> Vaccine Candidates Identified Through Infection-Informed Antigen Discovery.","authors":"Shea K Roe, Bo Zheng, Sunita Gulati, Sanjay Ram, Paola Massari","doi":"10.3390/vaccines14090798","DOIUrl":"10.3390/vaccines14090798","url":null,"abstract":"<p><p><b>Background:</b> The continued emergence of antimicrobial-resistant <i>Neisseria gonorrhoeae</i> highlights the urgent need for an effective vaccine. We evaluated the immunogenicity and vaccine potential of six new gonococcal conserved hypothetical proteins identified through our immunobioinformatics-based pipeline (Candidate Antigen Selection Strategy, CASS). <b>Methods:</b> NGO0588, NGO0694, NGO0757, NGO0861, NGO1438 and NGO1802 proteins were expressed in <i>E. coli</i>, purified, and used to immunize mice, adjuvanted with Alum and MPLA. Immunological analyses included quantitative and qualitative evaluation of antigen-specific antibody responses, cytokines, serum bactericidal activity (SBA), and protective efficacy in the mouse gonococcal vaginal colonization model. <b>Results:</b> The six antigens elicited robust antigen-specific IgG and IgM antibody responses against <i>N. gonorrhoeae</i>. Antisera to NGO0588, NGO0861, NGO1430 and NGO1802 were bactericidal against different gonococcal strains. IgG antibodies recognizing the antigens were detected in sera obtained from women with disseminated gonococcal infection, particularly against NGO1802, supporting immunogenicity in humans. Taking immunological and biochemical properties into consideration, NGO0861, NGO1438 and NGO1802 were combined in a trivalent vaccine formulation. The trivalent vaccine elicited robust antigen-specific and <i>N. gonorrhoeae</i>-reactive serum IgG and IgM, mucosal IgG, and higher SBA titers than each individual antigen. However, in the mouse gonococcal vaginal colonization model, vaccinated mice and adjuvant control mice did not show statistically significant differences in time to infection clearance or bacterial burdens. <b>Conclusions:</b> A multiantigen vaccine composed of NGO0861, NGO1438 and NGO1802 elicited antibodies that were functional in vitro but did not lead to protection in vivo. Immunological analyses in vitro and in vivo emphasize the importance of evaluating antigen and antibody quality and functional activity for vaccine target prioritization of next-generation gonococcal multicomponent vaccines.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanohydrogel Composite Vaccine Capable of Bypassing the Blood-Brain Barrier and Targeting Tumors for Glioblastoma Immunotherapy via Intranasal Immunization.","authors":"Dawei Dai, Shuo Han, Guangming Wang, Yongming Qiu, Ang Li","doi":"10.3390/vaccines14090797","DOIUrl":"10.3390/vaccines14090797","url":null,"abstract":"<p><p><b>Background</b>: Glioblastoma (GBM) is a primary malignant tumor of the central nervous system and has a high lethal rate despite therapeutic advances. Although immunotherapies have achieved great success in solid tumors, the highly immunosuppressive tumor microenvironment and the blood-brain barrier (BBB) obstruction hinder the development of immunotherapies for GBM. In this study, we innovatively developed a nanohydrogel composite vaccine (nanoCOM-GEL) for GBM immunotherapy via intranasal immunization. <b>Methods</b>: The nanoCOM-GEL used GelMA as the hydrogel matrix and was co-formulated with antigenic peptides, the BBB-penetrating peptide (peptide 22), as well as immune cell stimulants and chemokines. The efficiency of this vaccine in bypassing the BBB and its capacity to induce anti-GBM immune responses were evaluated in vitro and in vivo. <b>Results</b>: The nanoCOM-GEL vaccine demonstrated superior BBB-bypassing and BBTB-penetrating capabilities, potent immunostimulatory activity, and effective GBM-targeting efficacy, as validated in both cellular and animal models. In an orthotopic GBM mouse model (<i>n</i> = 8 per group), intranasal immunization with nanoCOM-GEL significantly extended median survival from 21 days (control group) to more than 60 days (nanoCOM-GEL group), representing a 2.8-fold increase (<i>p</i> < 0.001). The vaccine markedly inhibited tumor growth, as evidenced by an 82.5% reduction in tumor tissue at day 21 compared to controls (<i>p</i> < 0.01). Mechanistically, nanoCOM-GEL increased intratumoral CD8⁺ T cell infiltration by 9.5-fold and upregulated DCs by 6.4-fold, while simultaneously reducing intratumoral M2-type tumor-associated macrophages by 79.3% (<i>p</i> < 0.001), effectively reshaping the immunosuppressive tumor microenvironment. <b>Conclusions</b>: This innovative nanoCOM-GEL vaccine achieved potent anti-GBM therapeutic efficacy and provided a promising strategy for effective GBM immunotherapies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}