Development and validation of the Vaccine Barriers Assessment Tool for identifying drivers of under-vaccination in children under five years in Australia.

Data on routine childhood vaccination coverage can only tell us who is under-vaccinated; it cannot explain why vaccine coverage is low. Collecting data on the reasons behind under-vaccination is necessary to implement cost-effective strategies that address key barriers and target interventions appropriately. However, no instruments that measure both vaccine acceptance and access factors among parents of children <5 y have been validated in high-income countries. This study aims to develop and validate the Vaccine Barriers Assessment Tool (VBAT) for Australia. We applied three phases of mixed methods data collection and analysis. In Phase 1, we developed a comprehensive list of 80 items reflecting all potential parental barriers to childhood vaccination, derived from published literature and behavioral theory. Through cognitive interviews (n = 28), we refined this list to 45 items. In Phase 2, we conducted a two-wave online survey to test the reliability and validity of these items in an Australian sample of parents (n = 532) with structural equation modeling, further refining the list to 35 items. In Phase 3, we conducted a final parent survey (n = 156), administering these items along with the Parent Attitudes toward Childhood Vaccination (PACV) scale for comparison. We reviewed participants' immunization register data to assess the predictive validity of the proposed models. The final 6-item short form and 15-item long form Vaccine Barriers Assessment Tool assess access, communal benefit, personal risk, equity, commitment, social norms, and trust in health-care workers. It is being applied for national surveillance in Australia and will be adapted for additional populations and vaccines.

Vaccination decision-making among mothers of children 0-12 months old in Nigeria: A qualitative study.

The contribution of vaccination to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths annually. However, in Nigeria, vaccine-preventable-diseases still account for one-in-eight child deaths before their fifth-year birthday. Nigeria is one of the ten countries where 4.3 million children under five are without complete immunization. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. To conduct focus groups, a simplified quota sampling approach was used to select mothers of children 0-12 months old in four geographical clusters of Nigeria. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two concepts were added that had proved meaningful in previous work (religion and masculinity). The data were analyzed using a meta-aggregation approach. The sample was relatively positive toward vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community wellbeing (collective responsibility). They had a bias toward God as ultimate giver of good health (religion) and their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, hence, motivated vaccination (complacency). The study provided a useful qualitative tool for understanding mothers' vaccination decision-making in low resources settings.

Health Literacy and Health Care System Confidence as Determinants of Attitudes to Vaccines in France: Representative Cross-Sectional Study.

BACKGROUND: Health literacy involves individuals' knowledge, personal skills, and confidence to take action to evaluate and appraise health-related information and improve their health or that of their community. OBJECTIVE: This study aimed to analyze the association between health literacy and attitude toward vaccines, adjusted with other factors. METHODS: We used the SLAVACO Wave 3, a survey conducted in December 2021 among a sample of 2022 individuals, representative of the French adult population. We investigated factors associated with the attitude toward vaccines using respondents' different sociodemographic data, health literacy levels, and the health care system confidence levels using a multinomial logistic regression analysis. RESULTS: Among the participants, 440.4 (21.8%) were classified as "distrustful of vaccines in general," 729.2 (36.1%) were "selectively hesitant," and 852.4 (42.2%) were "nonhesitant." In our model, the level of health literacy was not statistically different between the "distrustful of vaccines in general" and the "selectively hesitant" (P=.48), but it was associated with being a "nonhesitant" (adjusted odds ratio [aOR] 1.86, 95% CI 1.25-2.76). The confidence in the health care system was a strong predictor for a "nonhesitant" attitude toward vaccines (aOR 12.4, 95% CI 7.97-19.2). We found a positive correlation of 0.34 (P<.001) between health literacy and confidence in the health care system, but the interaction term between health literacy and health care system confidence was not significant in our model. CONCLUSIONS: Health literacy was associated with a "nonhesitant" attitude toward vaccines. The findings demonstrated that health literacy and confidence in the health care system are modestly correlated. Therefore, to tackle the subject of vaccine hesitancy, the main focus should be on increasing the population's confidence and on increasing their health literacy levels or providing vaccine information addressing the needs of less literate citizens.

Adult vaccination against respiratory infections in Egypt: a review of expert opinions.

INTRODUCTION: Lower respiratory tract infection is one of the leading causes of morbidity and mortality all over the world, with a substantial impact on healthcare costs. In Egypt, local consensus on its burden, diagnosis, and vaccination is scarce. This expert opinion is the first to address the local recommendations for vaccinating adults against respiratory infection. It sheds light on the growing need to understand the barriers and underpublicized concept of adult vaccination in Egypt. AREAS COVERED: A collaborative multidisciplinary panel from Egypt developed an expert opinion-based suggestions/points, including epidemiology, microbiology, and highlights on vaccination in Egypt, as well as challenges and recommendations regarding adult vaccination. EXPERT OPINION: Adult vaccinations against respiratory infections are now recommended for high-risk people by all healthcare regulatory bodies. However, it was acknowledged that there may be hesitancy and concerns among patients; in addition, healthcare professionals' awareness about vaccination guidelines and benefits needs improvement. There are several strategies that could be implemented to enhance vaccine adherence in Egypt. These approaches encompass conducting community education programs, addressing the concerns of patients, and enhancing awareness among healthcare professionals through education, policy changes, and periodical reminders in each healthcare setting.

Nanogel-Mediated antigen delivery: Biocompatibility, immunogenicity, and potential for tailored vaccine design across species.

Nanotechnology has emerged as a promising avenue for enhancing the efficacy of vaccine delivery systems. This study investigates the utilization of nanogels as carriers for the model antigen ovalbumin, with a focus on in vivo assessments in equine and murine models. Nanogels, owing to their biocompatibility and tunable physicochemical properties, offer a versatile platform for efficient antigen encapsulation and controlled release. The encapsulation efficiency and physicochemical characteristics of ovalbumin-loaded nanogels were comprehensively characterized. In vitro biocompatibility was evaluated, finding excellent properties of these nanogels. In vivo evaluations were conducted on both equine and murine subjects, assessing immunogenicity through antibody and splenic cell response. Furthermore, the study propose the potential use of nanogels in tailoring immune responses through the modulation of antigen release kinetics. The results obtained in the in vitro assays showed an increase in the uptake of nanogels by APCs compared to free antigen (OVA). In mice, an absence of inflammatory response in the inoculation site was observed, without systemic damage in the evaluated organs. In addition, non-significant humoral response was found nor cellular proliferation and proinflammatory cytokine production, compared with a traditional adjuvant as aluminum hydroxide, in both animal models. These findings allow further insights into nanogel-based delivery systems and offer valuable insights into their application in various animal models. In conclusion, this research establishes the utility of nanogels as effective carriers for antigens-based vaccines, with interesting biocompatibility properties and highly taken affinity by antigen-presenting cells, without inducing inflammation at the injection site. The study underscores the potential of nanogel technology in revolutionizing vaccine design and highlights the importance of tailored approaches for diverse target species.

Evaluation of Th1/Th2, regulatory cytokines and transcriptional factor FoxP3 in sheep immunized with a partially protective and non-protective vaccine and challenged with Fasciola hepatica.

Gene expression for Th1/Th2 cytokines (IL-4 and IFN-É£), regulatory cytokines (TGF-ß and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-É£ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-É£ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-ß in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions.

Identifying effective vaccine champions: Findings from a national survey of primary care professionals.

BACKGROUND: Vaccine champions are common in primary care, but little is known about which champions are effective. METHODS: In 2022, we surveyed 2,144 US primary care professionals (PCPs) who reported working with vaccine champions. Respondents rated the champion with whom they worked most closely on their effectiveness at improving vaccination rates. RESULTS: About half (49 %) of PCPs perceived their closest champion as highly effective. PCPs perceived advanced practice providers and nursing staff as highly effective somewhat more often than physicians (52 % and 58 % vs 43 %, p <.001). Other correlates of perceived effectiveness included being a formally appointed versus informal champion, working extremely versus less closely with PCPs, and using a high (4-5) versus low (0-1) number of implementation strategies to improve vaccination rates (all p <.001). CONCLUSIONS: Results suggest vaccine champions may benefit from having formal roles and opportunities to work closely with colleagues to improve vaccination rates using multiple strategies.

The zebrafish as a potential model for vaccine and adjuvant development.

INTRODUCTION: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges. AREAS COVERED: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors in zebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunological reagents for challenge studies. 4) Systems vaccinology: Due to the availability of a well-referenced zebrafish genome, transcriptome, proteome, and epigenome, this model offers potential here. EXPERT OPINION: It remains unproven whether zebrafishes can be employed for testing and developing human vaccines. We are still at the hypothesis-generating stage, although it is possible to begin outlining experiments for this purpose. Through transgenic manipulation, zebrafish models could offer new paths for shaping animal models and systems vaccinology.

Perspectives on the Performance of the Ethiopian Vaccine Supply Chain and Logistics System after the Last Mile Delivery Initiative: A Phenomenological Study.

Uninterrupted availability of vaccines requires a robust vaccine supply chain and logistics system (VSCLS). With special focus on remote and underserved settings, we assessed the reach and bottlenecks of the Ethiopian VSCLS after the initiation of the last mile transition. We explored the perspectives of key stakeholders using a qualitative phenomenological study. More than 300 in-depth interviews and 22 focus group discussions were conducted. The study was sequentially implemented over two phases to understand the bottlenecks at national and regional (Phase I) and lower (Phase II) levels. After the transition, the Ethiopian Pharmaceutical Supply Service started supplying vaccines directly to health facilities, bypassing intermediaries. The transition reduced supply hiccups and enabled the health sector to focus on its core activities. However, in remote areas, achievements were modest, and health facilities have been receiving supplies indirectly through district health offices. By design, health posts collect vaccines from health centers, causing demotivation of health extension workers and frequent closure of health posts. Challenges of the VSCLS include artificial shortage due to ill forecasting and failure to request needs on time, lack of functional refrigerators secondary to scarcity of skilled technicians and spare parts, and absence of dependable backup power at health centers. Vaccine wastages owing to poor forecasts, negligence, and cold chain problems are common. The VSCLS has not yet sustainably embraced digital logistics solutions. The system is overstrained by frequent outbreak responses and introduction of new vaccines. We concluded that the transition has improved the VSCLS, but the reach remains suboptimal in remote areas.

Self-adjuvanting polymeric nanovaccines enhance IFN production and cytotoxic T cell response.

Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (-1.18 mV) following encapsulation, referred to as n(OVA)C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8+ T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.

Multifaceted therapeutic applications of biomimetic nanovaccines.

The development of vaccines has had a crucial role in preventing and controlling infectious diseases on a global scale. Innovative formulations of biomimetic vaccines inspired by natural defense mechanisms combine long-term antigen stability, immunogenicity, and targeted delivery with sustained release. Types of biomimetic nanoparticle (NP) include bacterial outer membrane vesicles (OMVs), cell membrane-decorated NPs, liposomes, and exosomes. These approaches have shown potential for cancer immunotherapy, and in antibacterial and antiviral applications. Despite current challenges, nanovaccines have immense potential to transform disease prevention and treatment, promising therapeutic approaches for the future. In this review, we highlight recent advances in biomimetic vaccine design, mechanisms of action, and clinical applications, emphasizing their role in personalized medicine, targeted drug delivery, and immunomodulation.

Adjuvants in cutaneous vaccination: A comprehensive analysis.

Skin is the body's largest organ and serves as a protective barrier from physical, thermal, and mechanical environmental challenges. Alongside, the skin hosts key immune system players, such as the professional antigen-presenting cells (APCs) like the Langerhans cells in the epidermis and circulating macrophages in the blood. Further, the literature supports that the APCs can be activated by antigen or vaccine delivery via multiple routes of administration through the skin. Once activated, the stimulated APCs drain to the associated lymph nodes and gain access to the lymphatic system. This further allows the APCs to engage with the adaptive immune system and activate cellular and humoral immune responses. Thus, vaccine delivery via skin offers advantages such as reliable antigen delivery, superior immunogenicity, and convenient delivery. Several preclinical and clinical studies have demonstrated the significance of vaccine delivery using various routes of administration via skin. However, such vaccines often employ adjuvant/(s), along with the antigen of interest. Adjuvants augment the immune response to a vaccine antigen and improve the therapeutic efficacy. Due to these reasons, adjuvants have been successfully used with infectious disease vaccines, cancer immunotherapy, and immune-mediated diseases. To capture these developments, this review will summarize preclinical and clinical study results of vaccine delivery via skin in the presence of adjuvants. A focused discussion regarding the FDA-approved adjuvants will address the experiences of using such adjuvant-containing vaccines. In addition, the challenges and regulatory concerns with these adjuvants will be discussed. Finally, the review will share the prospects of adjuvant-containing vaccines delivered via skin.

Characterizing regional drug delivery within the nasal airways.

INTRODUCTION: The nose has been receiving increased attention as a route for drug delivery. As the site of deposition constitutes the first point of contact of the body with the drug, characterization of the regional deposition of intranasally delivered droplets or particles is paramount to formulation and device design of new products. AREAS COVERED: This review article summarizes the recent literature on intranasal regional drug deposition evaluated in vivo, in vitro and in silico, with the aim of correlating parameters measured in vitro with formulation and device performance. We also highlight the relevance of regional deposition to two emerging applications: nose-to-brain drug delivery and intranasal vaccines. EXPERT OPINION: As in vivo studies of deposition can be costly and time-consuming, researchers have often turned to predictive in vitro and in silico models. Variability in deposition is high due in part to individual differences in nasal geometry, and a complete predictive model of deposition based on spray characteristics remains elusive. Carefully selected or idealized geometries capturing population average deposition can be useful surrogates to in vivo measurements. Continued development of in vitro and in silico models may pave the way for development of less variable and more effective intranasal drug products.

Completion of multidose vaccine series in early childhood: current challenges and opportunities.

PURPOSE OF REVIEW: Completion of all doses in multidose vaccine series provides optimal protection against preventable infectious diseases. In this review, we describe clinical and public health implications of multidose vaccine series noncompletion, including current challenges to ensuring children receive all recommended vaccinations. We then highlight actionable steps toward achieving early childhood immunization goals. RECENT FINDINGS: Although coverage levels are high for most early childhood vaccinations, rates of completion are lower for vaccinations that require multiple doses. Recent research has shown that lower family socioeconomic status, a lack of health insurance coverage, having multiple children in the household, and moving across state lines are associated with children failing to complete multidose vaccine series. These findings provide contextual evidence to support that practical challenges to accessing immunization services are impediments to completion of multidose series. Strategies, including reminder/recall, use of centralized immunization information systems, and clinician prompts, have been shown to increase immunization rates. Re-investing in these effective interventions and modernizing the public health infrastructure can facilitate multidose vaccine series completion. SUMMARY: Completion of multidose vaccine series is a challenge for immunization service delivery. Increased efforts are needed to address remaining barriers and improve vaccination coverage in the United States.

COVID -19: On the threshold of the fifth year. The situation in Spain / COVID-19: A las puertas del quinto año

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection. (AU)

Pese a haber salido de la situación de pandemia, la incidencia de episodios de COVID-19 ha aumentado recientemente en España, incluidos los casos pediátricos y los ingresos en Unidades de Cuidados Intensivos. Circulan entre nosotros diversas variantes recombinantes, particularmente la XBB surgidas de dos sublinajes Omicron BA.2 con mutaciones en los genes que codifican las proteínas de la espícula y que pudieran aumentar la unión al receptor ACE2 y ser más propensas al escape inmune. Frente a ellas, 3 empresas farmacéuticas han elaborado vacunas adaptadas al sublinaje XBB.1.5 que ya se encuentran disponibles para su administración en nuestro medio con riesgos que no deben ser diferentes a los de las vacunas mRNA previas y con relaciones beneficio/riesgos claramente favorables. Deben aplicarse a pacientes con potencial de mala evolución de COVID-19 y a los colectivos que tienen una particular relación de proximidad con ellos. Su aplicación debe ser entendida no sólo desde una perspectiva de conveniencia individual sino desde la de la responsabilidad colectiva. Lo más conveniente parece hacer una inmunización simultánea de COVID-19 y gripe en nuestro medio. En el aspecto terapéutico hay poco que esperar ahora mismo de los antisueros pero siguen estando disponibles e indicados los fármacos antivirales ya conocidos aunque su eficacia tendrá que reevaluarse por su impacto en poblaciones mayoritariamente inmunizadas y con pronóstico mejor que las de tiempos pasados. A nuestro juicio, es necesario seguir haciendo un uso razonable y puntual de mascarillas y otros medios no farmacológicos de protección. (AU)

Artificial viruses: A nanotechnology based approach.

OBJECTIVES: The main objective of this work was to review and summarise the detailed literature available on viral nanoparticle and the strategies utilised for their manufacture along with their applications as therapeutic agents. DATA ACQUISITION: The reported literature related to development and application of virus nanoparticles have been collected from electronic data bases like ScienceDirect, google scholar, PubMed by using key words like "viral nanoparticles", "targeted drug delivery" and "vaccines" and related combinations. RESULT: From the detailed literature survey, virus nanoparticles were identified as carriers for the targeted delivery. Due to the presence of nanostructures in virus nanoparticles, these protect the drugs from the degradation in the gastrointestinal tract and in case of the delivery of gene medicine, they carry the nucleic acids to the target/susceptible host cells. Thus, artificial viruses are utilised for targeted delivery to specific organ in biomedical and biotechnological areas. CONCLUSION: Thus, virus nanoparticles can be considered as viable option as drug/gene carrier in various healthcare sectors especially drug delivery and vaccine and can be explored further in future for the development of better drug delivery techniques.