Vaccines最新文献

Background/objectives: Trained innate immunity refers to the enhanced responsiveness of innate immune cells, particularly macrophages, following exposure to stimuli such as β-glucan or zymosan, enabling improved defense against unrelated pathogens. This phenomenon has been widely investigated to better understand host-pathogen interactions and to support the development of improved infection control strategies. This study evaluated whether these training stimuli could enhance the protective efficacy of attenuated or inactivated vaccine models against Brucella ovis and Listeria monocytogenes infection.

Methods: Trained innate immunity was induced in vivo using β-glucan or zymosan, and seven days later mice were vaccinated with attenuated or gamma-irradiated formulations and subsequently challenged with B. ovis or L. monocytogenes. Vaccine-induced protection and immune responses were assessed through multiple experimental approaches.

Results: β-glucan significantly reduced bacterial infection in vitro in bone-marrow-derived macrophages and in vivo in target organs compared with zymosan. Although β-glucan did not enhance the efficacy of the attenuated B. ovis ΔabcBA vaccine, it markedly reduced bacterial colonization in mice vaccinated with gamma-irradiated B. ovis. β-glucan also did not improve the efficacy of the gamma-irradiated L. monocytogenes vaccine; however, 50% of the trained and vaccinated mice showed no detectable bacterial recovery. Increasing the number of β-glucan doses negatively affected infection control, suggesting that overstimulation may impair trained immunity.

Conclusion: Trained innate immunity enhances the protective effect of inactivated experimental vaccines against B. ovis and L. monocytogenes, while exerting a detrimental influence on the efficacy of a live attenuated B. ovis vaccine model.

Objective: To evaluate the level of knowledge, attitudes, and practices of Hungarian general practitioners (GPs) concerning human papillomavirus (HPV) infection, cervical cancer prevention, and HPV vaccination, and to identify physician-level factors associated with proactive recommendation practices. Methods: A cross-sectional nationwide survey was conducted between 30 April and 1 June 2024. The online questionnaire was distributed to practicing Hungarian GPs listed in the National Health Insurance Fund database. Anonymous responses were collected on demographic data, knowledge of HPV transmission and oncogenic potential, awareness of vaccination guidelines, and clinical counseling habits. Descriptive and inferential statistical analyses were performed. A total of 413 responses were received. Results: Most respondents were female (72.6%) with an average of 22.4 ± 9.6 years of professional experience. Although 89.8% correctly identified the causal link between HPV and cervical cancer, only 56.2% were aware of the complete vaccination schedule recommended for adolescents initiating after age 15. Knowledge scores were significantly higher among female physicians, urban practitioners, and those with postgraduate preventive medicine training. While the overall attitude toward HPV vaccination was positive (mean 4.6/5), 38.4% of respondents reported parental hesitancy as a common barrier, often citing misinformation regarding vaccine safety (64.9%) and lack of perceived need for boys (58.7%). Regression analysis revealed that familiarity with WHO and national vaccination guidelines independently predicted proactive vaccine recommendation (β = 0.43, p < 0.001). Conclusions: Hungarian general practitioners demonstrate good baseline awareness of HPV and its oncogenic role; however, knowledge gaps persist regarding vaccination schedules and counseling practices. Enhancing continuous medical education and communication training could strengthen GPs' role as key advocates in HPV vaccine promotion.

Background/Objectives: African swine fever is currently the most devastating viral disease affecting domestic and wild suids, causing major economic losses and severe impacts on natural populations. Oral immunization could become an important tool to control the panzootic and support wild pig conservation. However, this requires safe and effective vaccines, baits accepted by target species, and vaccine reservoirs that reliably release the vaccine during bait intake while maintaining vaccine integrity. Methods: We evaluated different bait types and vaccine containers in four wild Suiformes species, including Eurasian wild boar. In the same wild boar, we assessed oral vaccination with the live attenuated vaccine candidate "ASFV-G-ΔI177L". Environmental monitoring approaches were applied to detect potential virus shedding, and vaccine immunogenicity and dissemination were evaluated. Vaccine stability was tested in vitro in two container types under different temperature conditions. Results: Bait uptake and container performance varied between manufacturers and among species. Environmental samples were largely negative for vaccine virus genome under controlled laboratory conditions, with only a few positive cotton ropes (0.43% of all samples). After oral bait vaccination, 45% (9/20) of wild boar seroconverted, with a higher proportion in animals receiving the vaccine in the slightly less attractive bait (gelatine-based). Vaccine virus dissemination was limited to a small number of organs, including gastrohepatic and mandibular lymph nodes. Conclusions: Our findings demonstrate that wild pigs can be vaccinated orally with "ASFV-G-ΔI177L" while virus shedding appears minimal. Although the tested baits show potential for multiple target species, baits and containers require optimization. Environmental monitoring methods also need refinement for field application.

Background/objectives: Vaccines targeting melanoma antigens can elicit CD8⁺ T cell responses, but a growing body of work suggests CD4⁺ T cells also play a role in tumor control. Induction of CD4⁺ cells may also support B cells in producing tumor antigen-specific antibodies (Abs). We investigated Abs induced by vaccination with a cocktail of six class II MHC-restricted melanoma peptides (6MHP) and the effect of adjuvant type on Ab isotypes. We hypothesized that the vaccines would induce Abs that respond to different epitopes on individual peptides and that IgG isotype distribution varies with different vaccine adjuvants.

Methods: Sera from patients who received a 6MHP vaccine were evaluated with enzyme-linked immunosorbent assays to map epitopes for polyclonal Ab responses to synthetic melanoma peptides. IgG isotypes of Ab responses to 6MHP were assessed in patients who received one of four adjuvants (Incomplete Freund's Adjuvant (IFA) alone, IFA + polyICLC, IFA + systemic metronomic cyclophosphamide (mCy), or IFA + polyICLC + systemic mCy) to characterize IgG isotype distribution.

Results: Epitope mapping revealed that at least 50% of patients had responses to two or more epitopes on the same peptide, suggesting polyclonal Ab responses. Serum evaluation for IgG isotypes showed predominant induction of IgG1 and IgG3. Mean total IgG was highest when IFA and polyICLC were used in combination. Patients who received TLR3 agonist polyICLC had significantly higher concentrations of total IgG, IgG1, and IgG3 compared to patients who did not receive polyICLC.

Conclusions: Vaccine-induced Abs may respond to multiple epitopes within the same peptide, warranting further studies into their ability to facilitate antigen uptake and presentation through the formation of large immune complexes. The findings also show that adding polyICLC to IFA can significantly enhance Ab responses. Collectively, this work underscores the immunologic potential of peptide-induced Abs and the importance of adjuvant selection in cancer vaccine design.

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living with HIV (PLWH). PLWH experience a disproportionate burden of HPV-related infection and HPV-related malignancies. Although HPV vaccines have been shown to be highly effective, vaccination coverage among PLWH remains suboptimal, particularly in low- and middle-income countries. Barriers to vaccination include extended dosing schedules, limited awareness of the vaccine, and misinformation. Evidence indicates HPV vaccines are safe and induce a robust antibody response in PLWH, especially among individuals with higher CD4+ cell counts and viral suppression on antiretroviral therapy. However, evidence for reduction in clinical HPV-related disease in this population remains limited. Ongoing research is aimed at optimizing the HPV vaccination schedule for PLWH and expanding vaccination in older, high-risk subgroups. Integrating HPV vaccination into HIV care is essential to reduce HPV-related morbidity and mortality in PLWH.

Objectives: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) merges multidrug resistance with hypervirulence, posing unprecedented therapeutic challenges. This study aimed to evaluate the efficacy of a recombinant fusion protein vaccine, KPC-Pal, designed to target both the carbapenemase KPC-2 and the virulence-associated peptidoglycan-associated lipoprotein Pal. Methods: The KPC-Pal fusion protein was constructed, expressed, and purified. Its protective efficacy was systematically assessed in a murine pneumonia model by measuring antigen-specific antibodies, cytokine profiles, and memory cell populations. The synergistic effect with the antibiotic meropenem was evaluated both in vitro and in vivo. Furthermore, the interaction with innate immune signaling via TLR2 was investigated. Results: Immunization with KPC-Pal conferred superior protection, resulting in significantly higher survival rates and reduced bacterial burdens in the lungs compared to immunization with either KPC-2 or Pal alone. It induced a robust Th2-biased humoral response and a mixed Th1/Th2/Th17 cellular immune profile, along with enhanced formation of tissue-resident memory T cells. Antibodies generated against KPC-Pal enhanced the efficacy of meropenem in vitro and in animal models, demonstrating a synergistic effect. While Pal alone strongly activated TLR2-driven inflammatory pathways, the KPC-Pal fusion selectively modulated MAPK signaling, mitigating excessive cytokine production. Additionally, KPC-Pal vaccination elicited cross-reactive antibodies against KPC-3 and KPC-33 variants. Conclusions: KPC-Pal functions as both an antigen and a self-adjuvant, offering a promising dual-target strategy for combating K. pneumoniae infections.

Background/objectives: Polysaccharide-protein conjugate vaccines have proven highly effective, yet they remain limited by manufacturing complexity, cost, and variable performance across serotypes, while carrier proteins can add unwanted immunological and production burdens. To address these constraints, we explored a carrier-protein-free conjugate vaccine concept in which a broadly MHC class II-binding helper epitope (PADRE) replaces the conventional protein carrier to provide T-cell help for a pneumococcal capsular polysaccharide antigen.

Methods: Using serotype 15C CPS as a model, we generated CPS-PADRE conjugates and compared designs with or without a putative cleavable motif (RR) at the junction, alongside a conventional protein conjugate as a benchmark.

Results: In mice, the CPS-protein conjugate induced the strongest CPS-specific IgG response, whereas CPS-PADRE conjugates elicited clear but overall lower antibody levels. Notably, incorporation of the cleavable motif did not improve immunogenicity and instead reduced humoral responses relative to the non-cleavable design.

Conclusion: These findings support the feasibility of carrier-protein-free polysaccharide-peptide conjugate vaccines, while highlighting that cleavable junctions are not universally advantageous and must be empirically optimized for polysaccharide-helper epitope architectures.

Background/Objectives: Low vaccination coverage and the persistence of zero-dose children remain the principal challenges for immunization efforts in Madagascar. To address these barriers, a socio-anthropological study was conducted to identify the determinants of both vaccination and non-vaccination in eight districts of the country. Methods: District selection was based primarily on immunization performance-specifically the proportion of zero-dose children-along with criteria of geographic and cultural diversity. A qualitative approach was employed, comprising 162 semi-structured individual interviews and 41 focus group discussions with key informants, including political-administrative, religious, and traditional authorities, healthcare workers, community health workers, and parents. Results: Overall, the benefits of vaccination were widely acknowledged by the population. Anti-vaccine rumors were found to be sporadic and, due to their provisional nature, potentially reversible even among those who relay them. Beyond conventional barriers such as scheduling constraints and limited accessibility, fluctuating motivation among community health workers and structural challenges affecting their work emerged as notable findings. Conversely, factors promoting vaccine acceptance were associated with trust in the vaccinators themselves and with a good understanding of vaccination-related issues, fostered through increased and context-specific sensitization efforts. Conclusions: In conclusion, no evidence was found to associate contexts such as rural settings or low-performing vaccination areas with lower vaccine acceptance. Similarly, anti-vaccine rumors were not confined to any particular category or group. Ultimately, the main obstacles are the prioritization of economic risk and concerns about potential side effects. The primary recommendation concerns strengthening awareness-raising efforts, while strengthening trust and improving the working conditions of community health workers.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. The management of HCC poses a major therapeutic challenge due to its pronounced molecular heterogeneity, frequent late-stage diagnosis, and intrinsic resistance to both conventional and modern therapeutic modalities. Furthermore, the relatively low tumor mutational burden and the presence of a profoundly immunosuppressive tumor microenvironment (TME) substantially limit the efficacy of immune-based interventions, particularly in advanced disease stages. In recent years, novel immunotherapeutic approaches-including immune checkpoint blockade (ICB), oncolytic virus therapy, and genetically engineered immune cell-based therapies-have garnered significant attention. Nevertheless, durable clinical responses and meaningful improvements in overall survival remain limited, underscoring the complexity of achieving effective immune control in HCC. Emerging evidence suggests that rational combination immunotherapy strategies may offer new therapeutic opportunities by overcoming immune resistance mechanisms. In this review, we provide a comprehensive overview of current therapeutic strategies for HCC, with particular emphasis on immunotherapeutic approaches. We discuss common clinical challenges spanning diagnosis to treatment resistance, critically evaluate key clinical trial outcomes, and highlight future directions aimed at improving therapeutic efficacy and long-term disease control.

Background/Objectives: Infant pneumococcal conjugate vaccines (PCV) have significantly reduced pneumococcal morbidity and mortality. Newer vaccines, 15-valent (PCV15) and 20-valent (PCV20), offer broader serotype coverage, potentially preventing more disease. This study estimated the number needed to vaccinate (NNV) to prevent one disease outcome for infant PCV20 and PCV15 programs versus 13-valent PCV (PCV13). Countries from Europe, the Asia-Pacific, and the Americas were included. Methods: A multi-cohort, population-based model estimated the cumulative NNVs for infant programs with PCV20 and PCV15 relative to PCV13 in 21 countries. Outcomes included overall pneumococcal case, hospitalization, and death. The ratio of PCV15 NNVs to PCV20 NNVs was calculated. Probabilistic sensitivity analysis (PSA) and scenario assessments tested results' robustness. Results: Across 21 countries, the median of country-specific NNV estimates to prevent one pneumococcal case was 13 with PCV20 and 80 with PCV15. Median NNVs to prevent a hospitalization or death were 44 and 568 with PCV20 and 203 and 2203 with PCV15, respectively. PCV20 demonstrated lower NNVs than PCV15 across all countries and outcomes. Median NNV ratios for PCV15 versus PCV20 were 5.1 (case), 4.5 (hospitalization), and 4.2 (death). No clear geographic differences were observed. PSA and scenario analyses indicated stable results with minimal deviations. Conclusions: Infant immunization with PCV20 is associated with lower NNVs than PCV15. To achieve the same disease reduction as PCV20, over five times as many children would need to be vaccinated with PCV15. These findings suggest PCV20 may offer greater public health impact compared with PCV15 in infant immunization programs.