Vaccine Delivery Research Articles

Improving the last mile delivery of vaccines through an informed push model: Experiences, opportunities and costs based on an implementation study in a rural district in Uganda.

Developing countries face challenges in ensuring equitable, timely, and efficient vaccine availability at health facilities. In Uganda, the distribution of vaccines from district stores to the last-mile health facilities is hindered by an unpredictable and unreliable mixed push-pull delivery system. This system often results in poor vaccine management, stock-outs, and missed vaccination opportunities. This pilot study aimed to enhance the efficiency of last-mile vaccine delivery by implementing an informed push model. The specific goals were to improve vaccine lead time, standardize cold chain management during transportation, and evaluate the costs of implementing the informed push model. A mixed methods approach was used to evaluate the impact of the informed push model in Gomba district, Uganda. Both quantitative and qualitative data were collected at baseline and endline. Quantitative data included mode, frequency, lead-time, and costs of vaccine delivery, vaccine stock status, and cold chain maintenance during transportation, gathered through semi-structured interviews. Qualitative data on experiences and challenges were collected using a guide. Descriptive statistics were used for quantitative data analysis, while an ingredients approach was used for costing data. Thematic analysis was applied to qualitative data. The informed push system significantly improved vaccine delivery efficiency and quality in Gomba district. The average lead-time for vaccine delivery reduced from 14 days at baseline to 5 days at endline. Timely vaccine receipt at health facilities increased from 36.8% to 100%. Temperature monitoring during transit improved from 26.3% to 100%. The proportion of facilities experiencing stock-outs dropped from 79.0% to 36.8%. Monthly distribution costs decreased from $494.8 ($0.07 per child) to $445.9 ($0.06 per child). The informed push model is a cost-effective strategy for improving last-mile vaccine delivery by reducing lead times, enhancing cold chain management, and decreasing stock-outs. Integration into the national immunization program is recommended for broader adoption in Uganda.

Vaccines are coming closer to you: the experience of the Corporate Healthcare Company (ASL) Rome 4

Abstract Issue The post-Covid period is characterised by vaccine fatigue and declining coverage, especially among children. Access to vaccination for adults and the elderly, outside of the influenza vaccination campaign, has historically been very low due to limited awareness of opportunities and difficulties in accessing vaccination centres. Description of the problem ASL Roma 4 is characterised by a dispersed population across a large territory of 28 municipalities, many of which are small and predominantly populated by elderly people. In order to reach this population, ‘proximity clinics’ were opened in 6 small municipalities in 2023, where the vaccination service offers a wide range of vaccines every 1-2 months. Since June 2023, two mobile vaccination units have also been used to extend the reach of vaccination activities. Results In 2023, vaccination activities at nearby clinics reached 343 people (166 males and 177 females), with a total of 473 vaccines administered. More than 70% of those vaccinated were over 65 years of age, including 47% over 80 years of age. Between September and December 2023, vaccination vans were deployed in high-traffic areas such as markets, supermarkets, squares, or in locations with hard-to-reach populations such as migrant reception centres, volunteer centres, and senior centres. As a result, 1183 people (585 men and 557 women) with an average age of 49 years were reached and 1699 vaccines were administered. 62% were over 65, 37% over 80, 41 were homeless and 87 were migrants. 56% of the vaccines administered were influenza and covid, but all types were provided. Lessons Although this method of vaccine delivery is still being implemented, its value lies mainly in vaccinating people who would not have voluntarily sought vaccination services, demonstrating the need to bring prevention as close to the user as possible. Key messages • The post-Covid period is characterised by vaccine fatigue and declining coverage. • It is necessary to bring vaccination prevention as close to the user as possible.

Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery.

Lipid nanoparticles (LNPs) have emerged as an effective and promising technology for messenger RNA (mRNA) delivery, offering a potential solution to physiological barriers and providing an alternative approach to gene therapy without the drawbacks associated with viral delivery. However, efficiently delivering mRNA remains a significant challenge in nucleic acid-based therapies due to the limitations of current LNP platforms in achieving optimal endosomal escape and mRNA release, which largely relies on finding a suitable ionizable lipid. Additionally, the synthesis of these ionizable lipids involves multiple chemical reactions, often making the process time-consuming and difficult to translate. In this study, we employed a facile, catalyst-free, and versatile one-pot multicomponent reaction (MCR) to develop a library of ionizable lipids featuring a pharmacologically significant tetrahydropyrimidine (THP) backbone, tailored for enhanced mRNA delivery. A library of 26 THP ionizable lipids was systematically synthesized in just 3 h and formulated with luciferase mRNA for initial in vitro screening. The THP LNPs exhibited tunable particle sizes, favorable ζ-potentials, and high encapsulation efficiencies. Among them, THP1 demonstrated the highest transfection efficiency both in vitro and in vivo after intramuscular administration, comparable to DLin-MC3-DMA (MC3), a conventional benchmark. Further optimization of THP1 with phospholipids significantly enhanced intramuscular mRNA delivery and showed sustained protein expression in vivo for up to 5 days. More importantly, it demonstrated successful intravenous delivery in a dose-dependent manner with minimal toxicity, as indicated by hematological, histopathological, and proinflammatory cytokine assessments. Furthermore, THP1 LNPs also demonstrated the ability to edit genes in specific liver tissues in a tdTomato transgenic mouse model, highlighting their precision and utility in targeted therapeutic applications. These findings position THP1 LNPs as promising candidates for advancing mRNA-based therapies, with significant implications for clinical translation in vaccine delivery and CRISPR/Cas9-mediated gene editing in the liver.

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Provider and community perceptions of integrated COVID-19 and routine childhood immunisation programmes in Nigeria: a qualitative exploratory study

BackgroundIn Nigeria, COVID-19 vaccines were delivered through outreach activities, as well as integrated within routine immunisation. However, evaluations of integrated approaches for novel vaccines are scarce. We aimed to understand the perceived benefits and challenges of integrating the COVID-19 vaccine within routine immunisation in Nigeria, and identify ways to strengthen this approach.MethodsWe conducted 30 semi-structured interviews with community members and healthcare workers in primary healthcare facilities (PHCs) in Jigawa (n = 16) and Oyo (n = 14) states, Nigeria from 08 August to 13 September 2022. Participants were selected purposively from PHCs. We obtained information on participants’ perception about routine immunisation, and perceived benefits and challenges associated with integrated COVID-19 vaccine delivery. Healthcare worker and community interviews were analysed separately following a thematic analysis approach.ResultsWe identified four themes that describe the community and healthcare workers’ responses, perceived impact, and the health system adaptions to the challenges associated with the integrated vaccine delivery approach. Community members expressed concern that children might be given COVID-19 vaccines instead of routine immunisations, while others appreciated the integrated approach due to their trust in the efficacy of COVID-19 vaccines, government, and healthcare providers. Healthcare providers perceived the integrated approach as improving vaccination coverage and awareness but noted additional problems of increased workload, vaccine scarcity, and prolonged clinic visits. Insufficient resources were subsisting barriers to effective integration in both states, but the provider’s gender was also a challenge in Jigawa state. Additionally, the use of incentives to generate demand had ambiguous effects in Jigawa state.ConclusionTaking an integrated approach to deliver COVID-19 vaccines was acceptable by healthcare providers but community members expressed concerns. Given existing vaccination programmes have persistent challenges, it is pertinent to address these barriers to enhance effectiveness of an integrated approach.

Iontophoresis and electroporation-assisted microneedles: advancements and therapeutic potentials in transdermal drug delivery.

Transdermal drug delivery (TDD) using electrically assisted microneedle (MN) systems has emerged as a promising alternative to traditional drug administration routes. This review explores recent advancements in this technology across various therapeutic applications. Integrating iontophoresis (IP) and electroporation (EP) with MN technology has shown significant potential in improving treatment outcomes for various conditions. Studies demonstrate their effectiveness in enhancing vaccine and DNA delivery, improving diabetes management, and increasing efficacy in dermatological applications. The technology has also exhibited promise in delivering nonsteroidal anti-inflammatory drugs (NSAIDs), treating multiple sclerosis, and advancing obesity and cancer therapy. These systems offer improved drug permeation, targeted delivery, and enhanced therapeutic effects. While challenges remain, including safety concerns and technological limitations, ongoing research focuses on optimizing these systems for broader clinical applications. The future of electrically assisted MN technologies in TDD appears promising, with potential advancements in personalized medicine, smart monitoring systems, and expanded therapeutic applications.

Advanced technologies for the development of infectious disease vaccines.

Vaccines play a critical role in the prevention of life-threatening infectious disease. However, the development of effective vaccines against many immune-evading pathogens such as HIV has proven challenging, and existing vaccines against some diseases such as tuberculosis and malaria have limited efficacy. The historically slow rate of vaccine development and limited pan-variant immune responses also limit existing vaccine utility against rapidly emerging and mutating pathogens such as influenza and SARS-CoV-2. Additionally, reactogenic effects can contribute to vaccine hesitancy, further undermining the ability of vaccination campaigns to generate herd immunity. These limitations are fuellingthe development of novel vaccine technologies to more effectively combat infectious diseases. Towards this end, advances in vaccine delivery systems, adjuvants, antigens and other technologies are paving the way for the next generation of vaccines. This Review focuses on recent advances in synthetic vaccine systems and their associated challenges, highlighting innovation in the field of nano- and nucleic acid-based vaccines.

Metal‐organic frameworks‐based nanomedicines to promote cancer immunotherapy: Recent advances and future directions

AbstractCancer immunotherapy uses the body's immune system to fight tumors by restoring natural antitumor responses. Metal‐organic frameworks (MOFs), characterized by their unique crystalline porous structures formed from metal ions linked by organic ligands, offer a promising solution. Recent studies have unveiled the potential of MOFs in cancer immunotherapy. The exceptional porosity and surface area, coupled with their extraordinary thermal and chemical stability, bring significant advantages for efficient drug loading and delivery of immunotherapeutic agents. The adaptability of MOFs further enhances the controlled release of immunotherapeutic drugs within target cells and increases tumor sensitivity to other therapies such as photodynamic, photothermal, and radiotherapy. This multifunctional carrier contributes to modulating the tumor microenvironment and reactivating antitumor immunity, providing a comprehensive strategy for cancer treatment. In this review, we summarize the applications of MOFs in immune checkpoint blockade, immunomodulator delivery, and cancer vaccine delivery, and discuss existing challenges in their use for immunotherapy. This discussion aims to offer insights for developing better treatments and enhancing the efficacy of immunotherapy.

The cost of COVID-19 vaccine delivery in Bangladesh

ABSTRACT COVID-19 vaccination has been instrumental in fighting the pandemic, but evidence on the actual costs associated with delivering these vaccines in resource-constrained settings has been limited. We estimated the cost of delivering COVID-19 vaccines in Bangladesh through five delivery strategies in 2021 and 2022, including Ministry of Health (MOH) hospitals, non-MOH government hospitals, outreach at Expanded Program on Immunization (EPI) centers, mass campaigns, and schools. This was a bottom-up costing study, estimating costs from a payer and beneficiary perspective. We also mapped the funding flows for COVID-19 vaccination activities and analyzed programmatic and financial challenges. The economic cost incurred by the health system to deliver COVID-19 vaccines was $1.05 per dose, excluding vaccine costs. This was made up of a financial cost of $0.29 per dose and an opportunity cost of $0.75 per dose. School-based delivery incurred the lowest financial cost of $0.27, while outreach at EPI centers incurred the highest at $0.44 per dose. The low financial cost per dose is attributed to the high daily volumes delivered at sampled sites, minimal additional resources provided to sites to implement the COVID-19 vaccination program, and a reliance on the existing workforce. Beneficiaries spent an average of $1.63 to receive a single dose of COVID-19 vaccination at fixed sites, with transport representing the largest cost driver ($0.75 per dose). The economic cost to receive one dose of the COVID-19 vaccine was $4.78. Findings can support the Government of Bangladesh to make efficient and equitable resource allocation decisions for vaccination programs.

Exploring the evolution of rotavirus vaccines and its impact on global public health

Rotavirus, a prevalent pathogen within the Reoviridae family, poses a significant threat to children, particularly infants and young children, causing gastroenteritis. High transmissibility and severe diarrhea lead to dehydration, severe infection, and death, especially in regions with limited resources and poor sanitation. Rotavirus infections spread through contaminated food, water, and fomites, primarily affecting developing countries due to inadequate sanitation standards. Vaccination has emerged as a crucial preventive strategy against rotavirus gastroenteritis, with the aim of reducing the global burden of the disease. The early rotavirus vaccines, exemplified by Rota-Shield, faced challenges such as safety concerns, emphasizing the importance of rigorous safety evaluation and post-marketing surveillance. Subsequent vaccines, Rotarix and RotaTeq, have shown efficacy and safety, significantly reducing rotavirus-related morbidity and mortality worldwide. The global implementation of rotavirus vaccination programs has expanded vaccine access, leading to a decrease in disease incidence and hospitalizations. Despite these achievements, challenges persist, such as hesitantness to apply the vaccine and disparities in vaccine access. Future research directions include the development of next-generation vaccines with greater coverage and the exploration of novel vaccine delivery strategies. A sustained commitment to research, infrastructure strengthening, and community involvement is essential to eliminate the burden of rotavirus disease worldwide. The objective of this review is to explore the evolution of rotavirus vaccines and impact on global public health.

The value of using COVID-19 antibody tests as a potential approach to prioritize vaccination delivery.

The highly contagious novel COVID-19 virus has demonstrated a great challenge for healthcare workers (HCWs) worldwide. One of these challenges is the availability of vaccines in some countries or societies, especially in the early stages of the pandemic. This study aims to determine the level of natural immunity against COVID-19 infection among HCWs exposed to COVID-19 at the early stages of the pandemic and build a model to determine the groups that can benefit more from the scarce vaccination resources. This study took place between January and March 2021, after the first waves of the COVID-19 pandemic, before spreading the variants of concern, such as the UK variant (Alpha B.1.1.7), and before starting the vaccine campaigns. This cross-sectional study collected serum samples from 251 vulnerable HCWs. The samples were tested for IgG antibodies against COVID-19 using commercial kits. The demographics and clinical characteristics of the participants were recorded using face-to-face interviews. COVID-19 IgG antibodies were detected in more than 40% of HCWs before vaccination. Those HCWs should have less priority than those without COVID-19 IgG. The seroprevalence of COVID-19 was higher in male HCWs and among nurses. There was no association between the participants' immunity and smoking status or different blood groups. Most HCWs reported being infected with the virus during the first wave, mainly at the end of 2020. A limited number of HCWs reported infections between January 2021 and March 2021. All HCWs eventually received the COVID-19 vaccine, ignoring being previously infected. The reported results emphasize the value of using immunity tests to prioritize the groups that may benefit the most from the limited vaccines, especially in developing countries with scarce resources where those with COVID-19 IgG antibodies should have less priority for the COVID-19 vaccine. The present results indicate that up to 40% of the delivered vaccines to HCWs who had COVID-19 antibodies could be prioritized more wisely in future pandemics.

Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Application of Controlled Release Mechanisms in Vaccine Delivery

Vaccines, as an essential means of preventive medicine, profoundly impact human health by stimulating an immune response to protect the body from pathogens or treat diseases. However, conventional vaccine delivery methods have limitations such as multiple injections, rapid degradation in vivo, and difficulty in targeted delivery. The development of controlled release mechanisms has overcome these challenges, optimized the immune response and improved the efficacy and safety of vaccines by precisely controlling the time, space and dose of vaccine release in vivo. This review explores the fundamentals, recent applications and future directions of controlled release mechanisms in vaccine delivery, focusing on the design and application of intelligent delivery systems such as biodegradable nanoparticles, self-healing microspheres, scaffolded vaccines and targeted vaccine systems. With the continuous progress of biotechnology and nanotechnology, controlled-release vaccines herald a new direction in vaccine design and delivery and bring efficient vaccine products to global public health.

To vaccinate or not to vaccinate? Experiences of COVID-19 vaccine uptake among people living with non-communicable diseases in Ghana: A qualitative study.

Following the development of a vaccine for COVID-19, the expectation was instantaneous widespread distribution and uptake to halt further spread, severe illness and deaths from the virus. However, studies show very low uptake, especially in resource-poor settings, and little is documented about the drivers of vaccine uptake in populations classified as high-risk. In this study, we explored access and uptake of COVID-19 vaccines among people living with non-communicable diseases (PLWNCDs) in Ghana. A qualitative study using in-depth interviews and focus group discussions was conducted among adults (>18 years) PLWNCDs stratified by sex, age, and type of non-communicable diseases (NCDs) at the community level (non-users of the health service) and health facility levels. Purposive sampling was used to select eligible participants. Topic guides were used to facilitate the face-to-face in-depth interviews and focus group discussions. The interviews and discussions were all digitally audio recorded. All transcripts and field notes were thematically analysed. Overall, 62 participants were recruited for this study. Family members, friends/peers, health workers and media were identified as the main sources of information for COVID-19 vaccines. Several barriers that mediated access to the COVID-19 vaccines in Ghana were reported including mistrust of vaccine efficacy and fears of vaccine side-effects, long distance to and waiting hours at vaccination centres, shortages of vaccines at vaccination centres and non-prioritization of NCD patients for the vaccine. To improve uptake, intensified education and sensitization, house-to-house vaccination, expansion of vaccination centers and increased supply of vaccines were recommended by participants. Compared to studies elsewhere, misinformation and disinformation were not major causes of vaccine hesitancy. If policymakers can improve community-based vaccine delivery, reduce queues and waiting times, prioritize PLWNCDs and other vulnerable groups, and improve sensitization and communication-our findings suggest there will be major improvements in COVID-19 vaccine coverage in Ghana.

Cost of COVID-19 vaccine delivery in nine States in Nigeria via the U.S. Government Initiative for Global Vaccine Access

BackgroundIn 2022, the U.S. Centers for Disease Control and Prevention collaborated with implementing partners, African Field Epidemiology Network and Sydani Group, to support COVID-19 vaccination efforts in Nigeria. To characterize the costs of COVID-19 vaccination, this study evaluated financial costs per dose for activities implemented to support the intensification campaign for COVID-19 vaccination.MethodsThis retrospective evaluation collected secondary data from existing expenditure and programmatic records on resource utilization to roll out COVID-19 vaccination during 2022. The study included incremental financial costs of the activities implemented to support an intensification campaign for COVID-19 vaccination across nine states and six administrative levels in Nigeria from the perspective of the external donor (U.S. Government). Costs for vaccines and injection supplies, transport of vaccines, and any economic costs, including government in-kind contributions, were not included. All costs were converted from Nigerian Naira to 2022 U.S. Dollars (US$).ResultsThe estimated financial delivery cost of the COVID-19 vaccination intensification campaign was US$0.84 per dose (total expenditure of US$6.29 million to administer 7,461,971 doses). Most of the financial resources were used for fieldwork activities (86%), followed by monitoring and supervision activities (8%), coordination activities (5%), and training-related activities (1%). Labor (58%) and travel (37%) were the resource inputs that accounted for the majority of the cost, while shares of other resource inputs were marginal (1% for each). Most labor costs (79%) were spent on payments for mass vaccination campaign teams, including pay-for-performance incentives. By administrative level, the largest share of costs (46%) was for pay-for-performance incentives at the community, health facility, or campus levels combined, followed by local government area level (24%), community level only (15%), state level (9%), national level (3%), campus level only (1%), and health facility level only (< 1%).ConclusionsFindings from the evaluation can help to inform resources needed for vaccination activities to respond to future outbreaks and pandemics in resource-limited settings, particularly to reach new target populations not regularly included in routine childhood immunization delivery.

MRNA vaccines: A powerful tool in cancer treatment

As an emerging immunotherapy, cancer vaccine is a method of introducing tumor antigens, genes encoding tumor antigens, immune cells and molecules into the body to activate specific immune responses to kill tumors. In April 2010, the world's first related drug, previz, was approved for marketing in United States. The drug extracts peripheral blood mononuclear cells from patients' autoimmune cells, activates them in vitro and then infuses them back into the treatment of asymptomatic or mildly symptomatic hormone-refractory advanced prostate cancer. mRNA vaccines have attracted much attention because of their high efficacy, specificity, versatility, ability to develop rapidly on a large-scale, low-cost production potential and safety. The mRNA vaccines and nano-agent delivery technology are considered to have great potential in cancer immunotherapy. In recent years, developments in the design and delivery methods of mRNA vaccines have accelerated the development and use of mRNA vaccinations against cancer in clinical settings. This review introduces optimization strategies of mRNA vaccinations against cancer, including coding and non-coding region optimization, and emphasizes mRNA vaccine delivery systems. Multiple nanoparticle vectors have currently been developed to improve mRNA stability and administration efficiency. At the same time, we discuss the applications of cancer therapy with mRNA vaccinations, its limitations and future challenges.

Overcoming Barriers to Childhood and Adolescent Vaccination: Opportunities in Precision Health Promotion

Abstract Background Vaccination remains one of the greatest success stories in public health as cost-effective interventions to reduce morbidity and mortality from infectious diseases at the population level. However, the COVID-19 pandemic created unprecedented challenges to the immunization sector. Uptake of routine childhood and adolescent vaccinations was forestalled by challenges related to pandemic lockdowns/quarantine, reduced patient-provider interactions, parental reluctance to seek preventative services, poor access to health services, and loss of income and/or health insurance. Compared to pre-pandemic estimations, the pandemic era brought a consequential decline in coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP). This study sought to address suboptimal adolescent vaccine delivery systems and bolster uptake in the post-pandemic era with the introduction of precision health promotion strategies centered around the use of Personal Health Libraries (PHL). Methods Leveraging artificial intelligence (AI), and semantic web technologies to integrate contextual knowledge (i.e., clinical, biomedical, and SDoH data) with patient preferences, proposed PHL platforms could aid in generating personalized evidence-based recommendations useful to both care provider promotion of vaccination and mitigating patient and caregiver hesitancy. The proposed application stands to provide customized digital health interventions by 1) facilitating remote knowledge acquisition, exchange, and visualization of the benefits of on-time vaccination, 2) improving health information-seeking behaviors to reduce hesitancy, 3) bolstering patient reminder and recall systems for follow-up and series completion, and 4) learning usage patterns to incorporate end-user preferences to empower patients, promote best practices, and enable them to make informed health decisions. Results The proposed PHL would serve as an ecosystem to manage and deliver tailored vaccine-related information to inform health decision-making regarding ACIP-recommended immunizations. Such a resource could administer health education and promotion that addresses common misconceptions regarding vaccination, alleviate safety, efficacy, and side effect concerns, and deliver evidence-based support of vaccines as primary protective measures (i.e., cancer prevention). Conclusion The use of PHL would enable rapid and real-time collection and interpretation of patient data beyond the traditional clinical setting, supplying care providers with tools for optimal vaccination recommendation to bolster uptake in the post-pandemic era. Moreover, the application would enable patients and caregivers to readily access vital health information and play a crucial role in addressing the obstacles encountered when seeking accurate and dependable vaccine-related information.

Discovery of Ketal-Ester Ionizable Lipid Nanoparticle with Reduced Hepatotoxicity, Enhanced Spleen Tropism for mRNA Vaccine Delivery.

The safety and efficacy of the lipid nanoparticle (LNP) delivery system are crucial for the successful development of messenger RNA vaccines. We designed and synthesized a series of ketal ester lipids (KELs), featuring a biodegradable ketal moiety in the linker and ester segments in the tail. Through iterative optimization of the head and tail groups of KELs, we tuned the pKa and molecular shapes, and identified (4S)-KEL12 as a safe and efficient ionizable lipid for mRNA delivery. (4S)-KEL12 LNP showed significantly higher delivery efficacy and lower toxicity than the DLin-MC3-DMA LNP. In comparison to SM-102 LNP, (4S)-KEL12 LNP exhibited better spleen tropism, reduced liver tropism, and hepatotoxicity. Additionally, (4S)-KEL12 demonstrated good biodegradability following intramuscular or intravenous injection. Notably, (4S)-KEL12 LNP encapsulated with a therapeutic mRNA cancer vaccine elicited robust cellular immune responses leading to substantial tumor regression along with prolonged survival in tumor-bearing mice. Our results suggest that (4S)-KEL12 LNP holds great promise for mRNA vaccine delivery. The comprehensive analysis of the structure-activity relationship, toxicity, biodegradability, distribution, expression, efficacy, and stereochemistry of these LNPs will greatly contribute to the rational design and discovery of novel lipid-based delivery systems.

Mannose and Lactobionic Acid in Nasal Vaccination: Enhancing Antigen Delivery via C-Type Lectin Receptors.

Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access. This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery. While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa. With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health.

Nasal Vaccine: A Special Prominence on SARS-CoV-2

Abstract: Nasal administration of mucosal medications and vaccines is an alternate and promising method of drug and vaccine delivery. Mucosal pathways can be used selectively for various disorders due to many benefits. Many initiatives are now being made to yield effective medications and cutting-edge nasal delivery systems. The structure of the nasal cavity and key features were discussed in this review. With a focus on vaccine distribution, the benefits, successes, and difficulties of using the nasal route for medical purposes were examined. The strong result supports the benefits and security, of the safety of nasal medication and vaccination administration. This alternate path may help many unmet medical needs and may also make big vaccination drives or expensive, protracted chronic therapies possible. Today, despite some lingering criticism, the area of nasal medicine and vaccine delivery is expanding quickly, supported by recent advancements in nanotechnology, imaging, and administration devices. The variety of drugs that have been licensed for nasal delivery is expected to increase significantly.