Human Vaccines & Immunotherapeutics最新文献

Kazakhstan planned to reintroduce the human papillomavirus (HPV) vaccine into the national vaccination calendar in 2024 for girls aged 12-14. A 2013 pilot attempt failed due to low acceptance. To inform implementation, we evaluated HPV vaccine knowledge and recommendation practices among primary healthcare workers (HCWs). In April-May 2023, we conducted a cross-sectional survey using convenience sampling among HCWs responsible for vaccination at 5 private and 29 of the largest public polyclinics in Almaty. Participants self-completed anonymous questionnaires. Knowledge scores >70% were considered adequate. We used logistic regression to assess factors associated with intention to recommend HPV vaccines, reporting adjusted odds ratios (OR) and 95% confidence intervals (CI). Among 832 participants, 68% were nurses, and 18% had >20 y experience. One-third (33%) had adequate HPV knowledge, 22% knew HPV has no cure, and 71% understood it is not airborne. One-fifth (20%) could dispel common HPV vaccine myths, 39% dispelled common childhood immunization myths, 61% correctly identified childhood vaccine contraindications, and 58% believed in childhood vaccines' safety and effectiveness. Overall, 28% would recommend the HPV vaccine to patients or their friends' children. Doctors were more likely to recommend than nurses (OR = 1.52, 95% CI = 1.06-2.18). Higher recommendation odds were also associated with ability to dispel childhood vaccines myths (OR = 1.47, 95% CI = 1.03-2.07), adequate HPV knowledge (OR = 1.63, 95% CI = 1.14-2.32), belief in vaccine safety (OR = 1.65, 95% CI = 1.12-2.47), and support for vaccinating HCWs (OR = 3.07, 95% CI = 2.11-4.54). HPV-related knowledge and recommendation intent among HCWs were low. Targeted training and communication may improve HPV vaccine uptake in Kazakhstan.

Seasonal influenza remains a major public health challenge in Qatar, causing significant morbidity and mortality among high-risk groups. Despite annual campaigns and free vaccines, coverage-rate is low, especially among children, the elderly, and pregnant women. This expert opinion review highlights vaccine-related epidemiological trends and barriers to uptake, including hesitancy, limited public awareness, logistical issues, and gaps in healthcare provider education in Qatar region. The panel underscores the urgent need for robust public education, targeted outreach, and empowering healthcare professionals to improve vaccine uptake. Special emphasis is placed on the role of live-attenuated-influenza-vaccine (LAIV), which allows needle-free administration, enhanced immunogenicity, and is suitable for school-based programs. Recommendations include expanding access via mobile clinics and schools, aligning procurement with seasonal peaks, and strengthening surveillance and quality systems. Adopting these strategies and empowering healthcare providers with necessary tools and knowledge can significantly improve influenza vaccination-coverage in Qatar and reinforce long-term public health resilience.

The problem of waning immunity is a major global concern of vaccine programs, with immunity against diseases such as COVID-19 (reduction in efficacy by ~25% in six months), pertussis (waning in 4-12 y), and influenza (annual updates needed) expected to decrease with time. While boosters reduce serious results in high-risk categories, these effects are short-term (4-6 months) and encourage global imbalances, where low-income areas lag in primary vaccination (<2%). Computational models have shown that primary vaccination in underserved regions prevents ~60% of hospitalizations worldwide, surpassing booster-focused measures (~47%). To maintain protection, variant-responsive boosters, rapid booster-design pipelines, universal vaccine platforms (including pan-coronavirus vaccines), and equity-based solutions (decentralized production) need to be integrated. Aligning with frameworks like the Immunization Agenda 2030 of the World Health Organization, plans should balance the expansion of high-risk groups while broadening primary access, providing infrastructure investment, and real-time surveillance to address evolving pathogens and systemic disparities.

Immune escape mechanisms critically restrict the efficacy of immunotherapy in lung cancer (LC), with only 20%-30% of patients responding to checkpoint inhibitors. To systematically map global trends and identify emerging hotspots, this study analyzed 2813 publications related to immune escape in LC immunotherapy from 1995 to 2025 (data retrieved August 9, 2025; analysis of annual trends uses complete year data through 2024) sourced from the Web of Science Core Collection database. Bibliometric visualization was performed using VOSviewer (version 1.6.19), CiteSpace (version 6.2.R3), and the biblioshiny R package. The dataset encompassed 75 countries, 3421 institutions, and 18,023 researchers across 693 journals. Publication trends delineated three distinct phases: an initial phase (1995-2010), an acceleration phase (2011-2018), and a maturation phase (2019-2024). China dominates in publication volume (1,382 papers) and total citations (45,657), whereas the University of Texas MD Anderson Cancer Center emerged as the most influential institution (n = 87). The Frontiers in Immunology recorded the highest number of publications (n = 155), while Cancer Research received the most co-citations (6,149). Li Zhang ranks as the most prolific author with 19 publications and 1251 citations, while R.S. Herbst holds the highest number of co-citations (n = 628). Current research clusters focus primarily on "therapeutic strategies and treatment integration," "tumor microenvironment characterization and immune cell dynamics," and "translational biomarkers and precision immunotherapy." Future research emphasizes "spatial microenvironment architecture," "computational predictive modeling," "alternative cell death pathways," "precision biomarker development," "hypoxia-immune interactions," and "stemness-EMT immune interfaces." Overall, the field's exponential growth and geographic disparities provide a structural foundation for developing strategies to overcome immune escape mechanisms by integrating spatial microenvironment characterization with advanced computational modeling.

Human Epidermal Growth Factor Receptor 2 (HER2) mutations account for approximately 3% of non-small cell lung cancer (NSCLC) patients. Currently, targeted therapies for HER2-mutant NSCLC include HER2 tyrosine kinase inhibitors (TKIs) and HER2 Antibody-drug conjugates (ADC). However, resistance often develops, and effective treatments for HER2 mutations remain lacking. We report a case of HER2-mutant lung adenocarcinoma where the patient developed resistance and severe interstitial lung disease following antibody-drug conjugate therapy. A highly biomimetic Human Organoid (HO) platform was employed to screen potential therapeutic options for the patient. The HO results indicated efficacy of Sunvozertinib and ineffectiveness of ADC, with maximum half-maximal inhibitory concentration (IC₅₀) values of 0.28 and 2.96, respectively. This case demonstrates the potential of Human Organoid Drug Sensitivity Test (HO-DST) to guide effective salvage therapy, bridging the gap between genomic profiling and functional drug response in precision oncology.

We previously demonstrated that native-like oligomers of Influenza A H1N1 M2e, expressed in Expi293F cells, elicit robust immune responses. Building on this foundation, we engineered a recombinant antigen comprising five tandem repeats of the M2e epitope (M2e-5x) fused to the tGCN4 domain, which promotes oligomerization and stability. BALB/c mice were immunized intramuscularly with M2e-5x antigen formulated in AddaVax^TM, in a prime-boost regimen, which elicited strong humoral and cellular responses. Despite this, vaccinated animals did not survive following high-dose lethal challenge with Influenza A/PR/8/34 (H1N1) and X-31 (H3N2) viruses. However, notable reductions in lung viral titers and less severe histopathological damage were observed compared to unvaccinated controls, suggesting partial viral clearance. Further evaluation of in vivo protective efficacy by combining M2e-5x (35 µg) with a low dose of soluble trimeric HA (5 µg) antigen showed complete protection in challenged mice. The overall results emphasized the importance of multi-antigen formulations for protective and robust influenza immunity. These findings highlight the importance of incorporating conserved and key viral epitopes into vaccine formulations to enhance broad and robust protection, providing valuable guidance for future influenza vaccine development.

Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs), ranging from mild to life-threatening. High-risk irAEs can lead to treatment discontinuation and higher mortality, though ICI-treated patients' death rate is under 5%. Currently, no reliable biomarkers predict irAEs' occurrence or severity. This study investigates the link between accessible biomarkers and high-risk irAEs in gastric cancer patients on ICIs, as well as to develop and assess a predictive model for such events. Data were collected from patients with gastric cancer who received ICIs therapy between May 2020 and March 2025. The incidence and risk factors associated with irAEs were analyzed using the chi-square test or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to develop a predictive model. This model was validated through 10-fold cross-validation and assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), calibration curves, and decision curve analysis. A total of 184 gastric cancer patients receiving ICIs therapy were enrolled in this study. The incidence of irAEs of any grade was 21.2%, while the incidence of grade ≥3 irAEs was 12.5%. Multivariate logistic regression analysis identified NLR-1 (p < .001), NLR2-1 (p < .001), PLR-1 (p = .001), tumor thickness (p = .018), CV (p = .001), and intratumoral necrosis (p = .028) as independent predictors of grade ≥3 irAEs. The AUC of the developed model was 0.878, with a sensitivity of 78.26%, specificity of 80.12%, PPV of approximately 80.95%, and NPV of approximately 75.52%. The corrected C-index, derived from bootstrap resampling, was 0.849, and both calibration curves and decision curve analysis confirmed good calibration and clinical utility. These predictors may aid risk stratification and optimized patient management.

Carriage of Neisseria meningitidis is essential in meningococcal transmission and is a prerequisite for invasive meningococcal disease (IMD). Meningococcal conjugate vaccines have been suggested to reduce acquisition of carriage in adolescents and young adults, contributing to herd protection. Mucosal immunity is considered key in protection against colonization. While mucosal antibody responses following parenteral meningococcal conjugate vaccination have been described in infants, adolescents and young adults, data in older adults, who are at increased risk for infectious diseases including IMD, are limited. This phase IV, open-label clinical trial (CTIS: 2024-513640-29-00) assessed antibody responses in saliva in 216 adults aged 65-85 y following primary meningococcal serogroup A, C, W, and Y conjugate vaccine (MenACWY-TT) vaccination. A booster dose was administered 1 y later in a sub-cohort (n = 100). MenACWY polysaccharide (ps)-specific IgA and IgG concentrations were measured in paired saliva and serum. Primary MenACWY-TT vaccination significantly increased salivary IgA and IgG concentrations for all serogroups. Salivary IgA concentrations returned to baseline within 1-2 y, whereas IgG concentrations remained elevated for at least 2 y. Booster vaccination enhanced salivary IgG concentrations, but failed to boost salivary IgA responses. Strong correlations were observed between post-vaccination salivary and serum IgG concentrations, and between salivary IgA and secretory component levels, suggesting systemic origin of IgG and mucosal origin of IgA. These findings highlight that MenACWY-TT vaccination induces durable salivary IgG and transient IgA responses in older adults, with limited enhancement of mucosal IgA after booster vaccination.

Nearly 85% of people will contract human papillomavirus (HPV) at some point in their lives. When given at the recommended ages, the HPV vaccine can prevent over 90% of HPV-related cancers. However, vaccination rates among young adults, including college students, remain low. Moreover, millions of international students enrolled in U.S. tertiary institutions may not have had access to preventive vaccines, including the HPV vaccine, in their countries of origin. This cross-sectional study conducted in October 2021, guided by the Theory of Planned Behavior (TPB), examined how attitudes, perceived behavioral control (PBC), and subjective norms relate to college students' intentions to receive the HPV vaccine. Conducted at a U.S. university, the study recruited 199 unvaccinated students through the university registrar's office and Amazon Mechanical Turk. Data were collected during the study period using an anonymous Qualtrics survey and analyzed using descriptive statistics, t-tests, and generalized linear models. We aimed to examine the influence of independent variables including attitude, subjective norms, and PBC, on the dependent variable, intention to receive the HPV vaccine. Of the 419 students who completed the survey, 199 (61 domestic and 138 international) who had not received the HPV vaccine were included in the study. The mean age of these participants was 21.27 y (SD = 3.29), with 135 males and 64 females. For both international and domestic students, attitudes toward HPV vaccination and subjective norms were significantly associated with higher vaccination intentions (international: attitude B = 0.11, p = .004; norms B = 0.38, p < .001; domestic: attitude B = 0.09, p = .027; norms B = 0.40, p < .001) in regression analyses. No significant differences were observed between the two groups in attitudes, perceived behavioral control, subjective norms, or vaccination intentions. These findings provide partial support for the TPB in explaining HPV vaccination intentions among college students. Public health initiatives and university-based programs may benefit from applying this framework by fostering positive attitudes and reinforcing supportive social norms. For routine practice, healthcare providers and campus health centers should integrate targeted education and outreach to improve vaccine uptake, particularly among international students. Future research should evaluate the effectiveness of TPB-based interventions in increasing actual vaccination rates and explore additional factors influencing vaccine intentions across diverse student populations.

Herpes zoster is caused by the reactivation of latent varicella-zoster virus (VZV), primarily affecting middle-aged and older individuals and often accompanied by severe pain and other complications. Vaccination is an effective preventive measure against this disease. In the present study, we evaluated the adjuvant activity of Toll-like receptor (TLR)9 and TLR7 agonists in combination with stimulator of interferon genes (STING) agonists for a VZV-glycoprotein E (gE)-based vaccine. Among the tested combinations, the CpG-2722 (TLR9 agonist) and 2'3'-c-di-AM(PS)2 (STING agonist) pairing exhibited potent immunostimulatory activity in immune cells and superior adjuvant activity for VZV-gE vaccines in a mouse models. Shingrix, a licensed herpes zoster vaccine, is administered intramuscularly. The CpG-2722/2'3'-c-di-AM(PS)2 combination adjuvanted VZV vaccine, administered intramuscularly, effectively induced higher gE-specific IgG responses than that induced by the Shingrix and imiquimod/2'3'-c-di-AM(PS)2 adjuvant vaccine. Notably, intranasal administration of the CpG-2722/2'3'-c-di-AM(PS)2 adjuvanted VZV vaccine to mice elicited a robust antigen-specific IgA response, which was barely detectable in intramuscularly administered vaccines. Two doses of the intranasal immunization, administered at a two-week interval, provided long-lasting protection, as antigen-specific IgG levels remained elevated for months without booster immunization. Further investigation into the functional mechanism revealed that CpG-2722 combined with 2'3'-c-di-AM(PS)2 induced a strong antigen-dependent T helper 1 (Th1) cytokine response, consistent with the antigen-independent cytokine-inducing properties of this adjuvant combination. This study demonstrates that the TLR9 and STING agonists formulated adjuvant induces a potent and long-lasting immune response, highlighting its potential as a promising adjuvant candidate for nasal VZV vaccines.