Search Results (1,558)

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

African, Caribbean, and Black (ACB) communities face increased COVID-19 morbidity and mortality, coupled with significant barriers to vaccine acceptance and uptake. Addressing these challenges requires innovative, multifaceted strategies. Peer-led interventions, grounded in critical health literacy (CHL) and critical racial literacy (CRL), and integrating collaborative equity learning processes, can enhance community capacity, empowerment, and health outcomes, contributing to long-term health equity. This paper describes and presents the evaluative outcomes of a peer-led intervention aimed at enhancing COVID-19 vaccine confidence and acceptance. The Peer-Equity Navigator (PEN) intervention consisted of a specialized training curriculum grounded in CHL and CRL. Following training, PENs undertook a 5-month practicum in community or health settings, engaging in diverse outreach and educational activities to promote vaccine literacy in ACB communities. The evaluation utilized a modified Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, using quantitative and qualitative methods to collect data. Sources of data included tracking records with community feedback, and a PEN focus group, to assess program feasibility, outreach, and effectiveness. From 16 September 2022, to 28 January 2023, eight trained PENs conducted 56+ community events, reaching over 1500 community members. Both PENs and community members reported high engagement, endorsing peer-led, community-based approaches and increased vaccine literacy. The PEN approach proves feasible, acceptable, and effective in promoting positive health behaviors among ACB communities. This intervention has clear implications for health promotion practice, policy, and research in equity-deserving communities, including immigrants and refugees, who also face multiple and intersecting barriers to health information and care. Full article

Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with administrative health records was conducted between September and October 2024 in Shenzhen, China. Participants were recruited through multistage random sampling. This analysis was based on a subsample of 996 parents whose children were 1–10 years old and without a prior history of chickenpox. Multivariate logistic regression models were fitted. Results: Among the participants, 47.0% reported that their children had received a varicella vaccination. Parents who believed that chickenpox was highly contagious (adjusted odds ratios [AOR]: 1.62, 95% confidence interval [CI]: 1.23, 2.13), perceived more benefits (AOR: 1.22, 95% CI: 1.05, 1.41) and cues to action (AOR: 1.33, 95% CI: 1.04, 1.69), and exhibited greater self-efficacy (AOR: 1.40, 95% CI: 1.09, 1.80) related to children’s varicella vaccination reported higher varicella vaccination uptake for their children. Greater perceived barriers related to vaccination (AOR: 0.89, 95% CI: 0.83, 0.95) and dysfunctional interactions with children (AOR: 0.97, 95% CI: 0.94, 0.99) were associated with lower varicella vaccination uptake for children. In addition, higher exposure to information encouraging parents to vaccinate their children against chickenpox (AOR: 1.24, 95%CI: 1.08, 1.41) and thoughtful consideration of the veracity of the information were associated with higher varicella vaccination uptake among children (AOR: 1.19, 95% CI: 1.05, 1.36). Conclusions: There is a strong need to promote varicella vaccination for children in China. Full article

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article

The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and resistance to treatment. Exploring the diverse roles of p53, which include regulating the cell cycle, repairing DNA, inducing apoptosis, reprogramming metabolism, and modulating immunity, provides valuable insights into cancer mechanisms and potential treatments. This review integrates recent findings on p53′s dual nature, functioning as both a tumor suppressor and an oncogenic promoter, depending on the context. Wild-type p53 suppresses tumors by inducing cell cycle arrest or apoptosis in response to genotoxic stress, while mutated variants often lose these functions or gain novel pro-oncogenic activities. Emerging evidence highlights p53′s involvement in non-canonical pathways, such as regulating tumor microenvironment interactions, metabolic flexibility, and immune evasion mechanisms. For instance, p53 modulates immune checkpoint expression and influences the efficacy of immunotherapies, including PD-1/PD-L1 blockade. Furthermore, advancements in precision diagnostics, such as liquid biopsy-based detection of p53 mutations and AI-driven bioinformatics tools, enable early cancer identification and stratification of patients likely to benefit from targeted therapies. Therapeutic strategies targeting p53 pathways are rapidly evolving. Small molecules restoring wild-type p53 activity or disrupting mutant p53 interactions, such as APR-246 and MDM2 inhibitors, show promise in clinical trials. Combination approaches integrating gene editing with synthetic lethal strategies aim to exploit p53-dependent vulnerabilities. Additionally, leveraging p53′s immunomodulatory effects through vaccine development or adjuvants may enhance immunotherapy responses. In conclusion, deciphering p53′s complex biology underscores its unparalleled potential as a biomarker and therapeutic target. Integrating multi-omics analyses, functional genomic screens, and real-world clinical data will accelerate the translation of p53-focused research into precision oncology breakthroughs, ultimately improving patient outcomes. Full article

Ensuring sustainable food systems is an urgent global priority as populations grow and environmental pressures mount. Technological innovations such as genetic engineering (GE) and nanotechnology (nano) have been promoted as promising pathways for achieving greater sustainability in agriculture and food production. Yet, the sustainability of these technologies is not defined by technical performance alone; it hinges on how they are perceived by key stakeholders and how well they align with broader societal values. This study addresses the critical question of how expert stakeholders evaluate the sustainability of GE and nano-based food and agriculture (agrifood) products. Using a multi-method online platform, we engaged 42 experts across academia, government, industry, and NGOs in the United States to assess six real-world case studies—three using GE and three using nano—across ten different dimensions of sustainability. We show that nano-based products were consistently rated more favorably than their GE counterparts in terms of environmental, economic, and social sustainability, as well as across ethical and societal dimensions. Like prior studies, our results reveal that stakeholders see meaningful distinctions between nanotechnology and biotechnology, likely due to underlying value-based concerns about animal welfare, perceived naturalness, or corporate control of agrifood systems. The fruit coating and flu vaccine—both nano-enabled—received the most positive ratings, while GE mustard greens and salmon were the most polarizing. These results underscore the importance of incorporating stakeholder perspectives in technology assessment and innovation governance. These results also suggest that responsible innovation efforts in agrifood systems should prioritize communication, addressing meaningful societal needs, and the contextual understanding of societal values to build trust and legitimacy. Full article

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

Vaccine adjuvants are non-immunogenic agents that enhance or modulate immune responses to co-administered antigens and are essential to modern vaccines. Despite their importance, few are approved for human use. The rise of new pathogens and limited efficacy of some existing vaccines underscore the need for more advanced and effective formulations, particularly for vulnerable populations. Aluminum-based adjuvants are commonly used in vaccines and effectively promote humoral immunity. However, they mainly induce a Th2-biased response, making them suboptimal for diseases requiring cell-mediated immunity. In contrast, saponin-based adjuvants from the Quillajaceae family elicit a more balanced Th1/Th2 response and generate antigen-specific cytotoxic T cells (CTL). Due to ecological damage and limited availability caused by overharvesting Quillaja saponaria Molina barks, efforts have intensified to identify alternative plant-derived saponins with enhanced efficacy and lower toxicity. Quillaja brasiliensis (A.St.-Hil. and Tul.) Mart. (syn. Quillaja lancifolia D.Don), a related species native to South America, is considered a promising renewable source of Quillajaceae saponins. In this review, we highlight recent advances in vaccine adjuvant research, with a particular focus on saponins extracted from Q. brasiliensis leaves as a sustainable alternative to Q. saponaria saponins. These saponin fractions are structurally and functionally comparable, exhibiting similar adjuvant activity when they were formulated with different viral antigens. An alternative application involves formulating saponins into nanoparticles known as ISCOMs (immune-stimulating complexes) or ISCOM-matrices. These formulations significantly reduce hemolytic activity while preserving strong immunoadjuvant properties. Therefore, research advances using saponin-based adjuvants (SBA) derived from Q. brasiliensis and their incorporation into new vaccine platforms may represent a viable and sustainable solution for the development of more less reactogenic, safer, and effective vaccines, especially for diseases that require a robust cellular immunity. Full article

Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. Receptor for hyaluronan-mediated motility (RHAMM) has emerged as a multifunctional regulator in cancer, contributing to cell motility, invasion, proliferation, and fibrosis. In addition to being regulated by non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, RHAMM serves as a promising therapeutic target. Recent developments in RHAMM-targeted strategies include function-blocking peptides (e.g., NPI-110, NPI-106, and P15-1), hyaluronan (HA) oligomers, and anti-RHAMM antibodies, all shown to modulate tumor stroma and suppress tumor invasiveness. Importantly, RHAMM-targeted peptide vaccines, such as the RHAMM-R3 epitope, have demonstrated immunogenicity and anti-leukemia efficacy in both pre-clinical and early clinical studies, suggesting their potential to elicit specific CD8⁺ T-cell responses and enhance graft-versus-leukemia effects. This review summarizes the intricate roles of RHAMM in cancer progression, its modulation by ncRNAs, and the translational promise of novel RHAMM-targeting approaches, providing insights into future directions for precision cancer therapy. Full article

(1) Background: Human Papillomavirus (HPV)-associated oropharyngeal cancer is the fastest-growing head and neck malignancy, yet vaccination coverage remains suboptimal. (2) Methods: In this cross-sectional survey conducted from April 2022 to April 2023, 400 parents of patients aged 8–18 years (mean ± SD = 12.8 ± 2.6; 59.3% female) reported their child’s HPV vaccination status and willingness to initiate or complete the vaccine series at a dental clinic. For those who were not fully vaccinated, reasons for refusal were documented. (3) Results: Over half (54.5%, n = 218) of the children were not fully vaccinated. Notably, 21% (46/218) of parents indicated an immediate willingness to vaccinate their child if the dentist offered it—a significant potential for improvement compared to general healthcare settings. Reported barriers included preference for a physician’s office (43.6%), indecision (20.3%), unspecified concerns (14.5%), safety worries (8.1%), and religious objections (5.2%). Male and younger patients (9–11 years) showed significantly lower vaccination coverage (p < 0.05). (4) Conclusions: Dentists can substantially impact public health by integrating immunization counseling, interprofessional collaboration, and vaccine administration, thereby addressing critical gaps in HPV-related cancer prevention. These findings highlight the opportunity for dental offices to enhance vaccination rates and prompt further research, education, and policy initiatives to advance the oral and general health of our patients. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article

COVID-19 vaccine hesitancy in Pakistan is a barrier to optimal vaccine uptake and has been situated within a context of hesitancy towards other vaccines. A mixed-methods study was conducted during the initial COVID-19 vaccine roll-out in 2021 in four union councils in Peshawar, consisting of a cross-sectional survey, eight focus group discussions (FGDs) with community members and eight in-depth interviews with healthcare workers (HCWs) to assess perceptions toward vaccines. Multivariable logistic regression was used to assess factors associated with COVID-19 vaccine hesitancy. Of 400 survey participants, 57.3% were vaccine acceptant and 42.8% vaccine hesitant. Just over half (56.8%) perceived COVID-19 vaccines to be safe. Most (88%) reported trust in HCWs to provide accurate vaccine information. FGDs revealed that women received less information about the vaccine compared to men and cultural restrictions were barriers even for those willing to be vaccinated. Correlates of vaccine acceptance included male sex (aOR 2.25; 95% CI 1.29–3.91), age 50 years or greater (aOR 1.74; 95% CI 1.19–6.31), social network support (e.g., vaccine acceptance among an individual’s social network) in receiving COVID-19 vaccines (aOR 2.38; 95% CI 1.45–3.89), community concern about COVID-19 spread (aOR 2.84; 95% CI 1.73–4.66), and trust in HCWs to provide vaccine information (aOR 3.47; 95% CI 1.62–7.42). Future vaccine promotion should prioritize engaging community leaders, sharing transparent information, combatting misinformation and rumors, and implementing household-based interventions especially targeting the importance of vaccination among women and young people to increase uptake. Full article

Background/Objective: Maternal immunization is highly recommended, particularly in developed countries. However, its awareness among pregnant women in Japan remains low. This study aimed to assess the awareness and attitudes toward maternal immunization among pregnant women in Japan and to identify the factors that may promote its acceptance. Methods: We conducted a cross-sectional questionnaire survey among pregnant women attending antenatal checkups at nine facilities in Kanagawa Prefecture, Japan, from August 2024 to January 2025. The survey assessed knowledge and intention regarding maternal immunization for influenza, pertussis, respiratory syncytial virus (RSV), and group B streptococcus (GBS) as well as attitudes toward vaccination costs and information sources. Results: Overall, 523 respondents were included in this study. The overall awareness of maternal immunization was 16%. Willingness to receive vaccinations during pregnancy was reported for influenza (68%), pertussis (58%), RSV (59%), and GBS (71%). A common reason for vaccine hesitancy included uncertainty about its effects on the fetus. The key factors associated with vaccine acceptance were higher educational attainment and prior knowledge of maternal immunization. Regarding costs, most respondents were willing to pay up to JPY 5000 (approximately USD 35). The most frequently prioritized sources were explanations from physicians, followed by explanations from midwives. Conclusions: Despite low awareness, vaccination intention was comparable to that reported in other countries. Points that may contribute to improved vaccine uptake were also identified. These findings may lead to the prevention of infectious diseases in newborns and infants in Japan and possibly improve public health. Full article

Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4⁺ and CD8⁺ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission. Full article