Vaccine Delivery Research Articles

Drivers of success in global health outcomes: A content analysis of Exemplar studies.

Applying a positive outlier lens is one effective approach for generating evidence to inform global health policy, program, and funding decisions. Exemplars in Global Health (EGH) is a program that studies positive outlier countries that have made extraordinary progress in health outcomes (despite limited resources) and disseminates their successes through multiple types of outputs. To date, EGH has studied, or is studying, 14 global health topics in 28 countries. This paper aims to identify findings, summarized as themes and sub-themes, that appear among all completed EGH studies. We developed a conceptual framework and used a content analysis approach to identify the top thematic areas that appear as drivers for programmatic success across EGH studies that were completed between June 2020-May 2023. The EGH studies (N = 31) spanned six topics including under-five child mortality (n = 6), childhood stunting (n = 5), community health workers (CHW) (n = 4), vaccine delivery (n = 3), COVID-19 response (n = 6), and newborn and maternal mortality reduction (n = 7) across 19 countries in sub-Saharan Africa, Latin America, South and Central Asia, and the Caribbean regions. Top drivers of success were defined as those critical or catalytic in achieving the intended outcome. Eight key drivers were identified: (1) efficient data collection and use for decision-making, (2) strong political commitment and health leadership, (3) effective stakeholder coordination, (4) a local, connected, and capacitated workforce, (5) intentional women's empowerment and engagement, (6) effective adoption and implementation of national policies, (7) effective and sustainable financing, and (8) equitable, efficient outreach and targeting. These cross-cutting drivers span a broad range of development outcomes, sectors, and populations, and indicate a need to effectively integrate people, systems, and sectors to improve global health outcomes. Findings from this study aim to support peer learning among countries and support evidence-based decision-making for funders, policymakers, and other key stakeholders.

Construction of lymph nodes-targeting tumor vaccines by using the principle of DNA base complementary pairing to enhance anti-tumor cellular immune response

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.Graphical

Immunization and Screening Methods for Cervical Carcinoma in Developing Nations: A Detailed Review

Objective: Cervical cancer remains a significant public health challenge in developing countries, disproportionately affecting women in these regions due to limited access to effective screening and vaccination programs. This review synthesizes the current literature on the implementation strategies, effectiveness, and challenges of cervical cancer screening and Human Papillomavirus (HPV) vaccination programs in developing countries, aiming to highlight successful models and identify gaps in current practices. Screening, for cervical cancer in developing countries faces numerous obstacles, including logistical challenges, lack of awareness, and insufficient healthcare infrastructure. Despite these hurdles, strategies such as single-visit approaches, leveraging low-cost HPV DNA testing, and utilizing mobile health units have shown promise in increasing screening coverage and early detection rates. The prerequisites for effective screening highlighted include affordability, cultural acceptability, and the ability to implement large-scale screening with limited resources. HPV vaccination presents a primary prevention measure with the potential to significantly reduce the incidence of cervical cancer. However, vaccination programs in developing countries encounter challenges in vaccine procurement, distribution, and achieving high coverage rates among the target population. Innovations in vaccine delivery, education campaigns to raise awareness, and partnerships with international health organizations are crucial for overcoming these barriers.This comprehensive review underscores the need for a multifaceted approach to cervical cancer prevention in developing countries, encompassing improvements in screening and vaccination strategies, health system strengthening, community engagement, and international collaboration. By learning from successful models and addressing identified gaps, there is a significant opportunity to reduce the burden of cervical cancer in these regions and move closer to achieving global health equity.

A glucan-particle based tularemia subunit vaccine induces T-cell immunity and affords partial protection in an inhalation rat infection model.

Tularemia is a zoonotic disease caused by the facultative intracellular gram-negative bacterium Francisella tularensis. F. tularensis has a very low infection dose by the aerosol route which can result in an acute, and potentially lethal, infection in humans. Consequently, it is classified as a Category A bioterrorism agent by the US Centers for Disease Control (CDC) and is a pathogen of concern for the International Biodefence community. There are currently no licenced tularemia vaccines. In this study we report on the continued assessment of a tularemia subunit vaccine utilising β-glucan particles (GPs) as a vaccine delivery platform for immunogenic F. tularensis antigens. Using a Fischer 344 rat infection model, we demonstrate that a GP based vaccine comprising the F. tularensis lipopolysaccharide antigen together with the protein antigen FTT0814 provided partial protection of F344 rats against an aerosol challenge with a high virulence strain of F. tularensis, SCHU S4. Inclusion of imiquimod as an adjuvant failed to enhance protective efficacy. Moreover, the level of protection afforded was dependant on the challenge dose. Immunological characterisation of this vaccine demonstrated that it induced strong antibody immunoglobulin responses to both polysaccharide and protein antigens. Furthermore, we demonstrate that the FTT0814 component of the GP vaccine primed CD4+ and CD8+ T-cells from immunised F344 rats to express interferon-γ, and CD4+ cells to express interleukin-17, in an antigen specific manner. These data demonstrate the development potential of this tularemia subunit vaccine and builds on a body of work highlighting GPs as a promising vaccine platform for difficult to treat pathogens including those of concern to the bio-defence community.

In Vivo Delivery of Spherical and Cylindrical In Vitro Reconstituted Virus-like Particles Containing the Same Self-Amplifying mRNA.

The dramatic effectiveness of recent mRNA (mRNA)-based COVID vaccines delivered in lipid nanoparticles has highlighted the promise of mRNA therapeutics in general. In this report, we extend our earlier work on self-amplifying mRNAs delivered in spherical in vitro reconstituted virus-like particles (VLPs), and on drug delivery using cylindrical virus particles. In particular, we carry out separate in vitro assemblies of a self-amplifying mRNA gene in two different virus-like particles: one spherical, formed with the capsid protein of cowpea chlorotic mottle virus (CCMV), and the other cylindrical, formed from the capsid protein of tobacco mosaic virus (TMV). The mRNA gene is rendered self-amplifying by genetically fusing it to the RNA-dependent RNA polymerase (RdRp) of Nodamura virus, and the relative efficacies of cell uptake and downstream protein expression resulting from their CCMV- and TMV-packaged forms are compared directly. This comparison is carried out by their transfections into cells in culture: expressions of two self-amplifying genes, enhanced yellow fluorescent protein (EYFP) and Renilla luciferase (Luc), packaged alternately in CCMV and TMV VLPs, are quantified by fluorescence and chemiluminescence levels, respectively, and relative numbers of the delivered mRNAs are measured by quantitative real-time PCR. The cellular uptake of both forms of these VLPs is further confirmed by confocal microscopy of transfected cells. Finally, VLP-mediated delivery of the self-amplifying-mRNA in mice following footpad injection is shown by in vivo fluorescence imaging to result in robust expression of EYFP in the draining lymph nodes, suggesting the potential of these plant virus-like particles as a promising mRNA gene and vaccine delivery modality. These results establish that both CCMV and TMV VLPs can deliver their in vitro packaged mRNA genes to immune cells and that their self-amplifying forms significantly enhance in situ expression. Choice of one VLP (CCMV or TMV) over the other will depend on which geometry of nucleocapsid is self-assembled more efficiently for a given length and sequence of RNA, and suggests that these plant VLP gene delivery systems will prove useful in a wide variety of medical applications, both preventive and therapeutic.

Leveraging machine learning for vaccine distribution in resource-limited settings: A synthesis of approaches

 Vaccine distribution in resource-limited settings remains a crucial global health challenge, exacerbated by factors such as inadequate infrastructure, limited resources, and complex supply chains. Leveraging machine learning (ML) holds promise for optimizing distribution efficiency and ensuring equitable access to life-saving vaccines. This paper synthesizes various ML approaches aimed at addressing vaccine distribution challenges in resource-constrained environments. The literature review examines existing research on ML applications in healthcare and vaccine distribution, highlighting key findings and methodologies. Methodologically, criteria were established for selecting relevant studies, with a focus on ML techniques and their effectiveness in resource-limited contexts.  Key ML approaches identified include predictive analytics for demand forecasting, route optimization algorithms for efficient vaccine delivery, and decision support systems for prioritizing distribution efforts. Case studies illustrate successful ML implementations in real-world settings, showcasing improved vaccine coverage and reduced wastage. Despite promising results, challenges persist, including data scarcity, model generalization, and ethical considerations. Future research directions include enhancing data collection methods, refining ML algorithms for specific contexts, and integrating ML solutions into existing healthcare systems. In conclusion, this synthesis underscores the transformative potential of ML in revolutionizing vaccine distribution in resource-limited settings. By addressing logistical barriers and optimizing resource allocation, ML-driven approaches offer a pathway towards achieving universal immunization coverage and mitigating the impact of infectious diseases on vulnerable populations. Keywords:  Machine Learning, Vaccine Distribution, Resource-Limited Settings, Synthesis of Approaches.

Conspiracy Theories, Vaccine Hesitancy and Determinants of Vaccination Acceptance in Nigeria: A Conceptual Review

Purpose: This conceptual review aims to dissect the intricate web of conspiracy theories, vaccine hesitancy and determinants of vaccination acceptance within Nigeria's socio-cultural context, shedding light on their genesis, propagation and impact on public health outcomes. Methodology: Employing a multidisciplinary approach, this study synthesizes existing literature and theoretical frameworks from various disciplines, including sociology, anthropology, public health, and communication studies. Methodological rigor is ensured through comprehensive literature review and critical appraisal of relevant studies, enabling a holistic exploration of the subject matter. Findings: Through a systematic analysis, the review identifies and examines socio-cultural, economic and political influences that shape vaccination behavior in Nigeria. It illuminates the multifaceted determinants contributing to vaccine hesitancy, ranging from religious beliefs to historical legacies to socio-economic factors and healthcare accessibility challenges. The review also highlights the genesis and propagation of conspiracy narratives, their impact on public trust in vaccination and consequent implications for immunization uptake. Unique Contribution to Theory, Policy and Practice: This review makes several contributions to theory, policy, and practice in the field of vaccination and public health. Firstly, it advances theoretical understanding by synthesizing existing knowledge and proposing conceptual frameworks that elucidate the socio-cultural, economic, and political determinants of vaccination behavior in Nigeria. Secondly, it informs policy development by identifying key areas for intervention, such as addressing vaccine hesitancy, countering misinformation, and strengthening healthcare infrastructure to enhance vaccine delivery. Finally, it offers practical insights for public health practitioners and policymakers, providing evidence-based recommendations for designing effective vaccination campaigns, communication strategies, and community engagement initiatives tailored to the Nigerian context.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus

The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Farmer‐friendly delivery of veterinary services: Experimental insights from the Kenyan dairy sector

AbstractPoor health conditions of livestock cause sizeable losses for many farmers in the Global South. Veterinary services, including vaccinations, could help but often fail to reach farmers under typical smallholder conditions. Here, we examine how the provision of a vaccine against East Coast Fever (ECF)—a tick‐borne disease affecting cattle in Africa—can be designed to reduce typical adoption barriers. Using data from a choice experiment with dairy farmers in Kenya, we evaluate farmers' preferences and willingness to pay for various institutional innovations in vaccine delivery, such as a stronger role of dairy cooperatives, new payment modalities with a check‐off system, vaccination at farmers' homestead, and bundling vaccinations with discounts for livestock insurance. Our data reveal that farmers' awareness of the ECF vaccine is limited and adoption rates are low, largely due to institutional constraints. Results from mixed logit and latent class models suggest that suitable institutional innovations—tailored to farmers' heterogeneous conditions—could significantly increase adoption. This general finding likely also holds for other veterinary technologies and services in the Global South.

Driving delivery and uptake of catch-up vaccination among adolescent and adult migrants in UK general practice: a mixed methods pilot study

BackgroundMigrants in the UK and Europe face vulnerability to vaccine-preventable diseases (VPDs) due to missed childhood vaccines and doses and marginalisation from health systems. Ensuring migrants receive catch-up vaccinations, including MMR, Td/IPV, MenACWY, and HPV, is essential to align them with UK and European vaccination schedules and ultimately reduce morbidity and mortality. However, recent evidence highlights poor awareness and implementation of catch-up vaccination guidelines by UK primary care staff, requiring novel approaches to strengthen the primary care pathway.MethodsThe ‘Vacc on Track’ study (May 2021–September 2022) aimed to measure under-vaccination rates among migrants in UK primary care and establish new referral pathways for catch-up vaccination. Participants included migrants aged 16 or older, born outside of Western Europe, North America, Australia, or New Zealand, in two London boroughs. Quantitative data on vaccination history, referral, uptake, and sociodemographic factors were collected, with practice nurses prompted to deliver catch-up vaccinations following UK guidelines. Focus group discussions and in-depth interviews with staff and migrants explored views on delivering catch-up vaccination, including barriers, facilitators, and opportunities. Data were analysed using STATA12 and NVivo 12.ResultsResults from 57 migrants presenting to study sites from 18 countries (mean age 41 [SD 7.2] years; 62% female; mean 11.3 [SD 9.1] years in UK) over a minimum of 6 months of follow-up revealed significant catch-up vaccination needs, particularly for MMR (49 [86%] required catch-up vaccination) and Td/IPV (50 [88%]). Fifty-three (93%) participants were referred for any catch-up vaccination, but completion of courses was low (6 [12%] for Td/IPV and 33 [64%] for MMR), suggesting individual and systemic barriers. Qualitative in-depth interviews (n = 39) with adult migrants highlighted the lack of systems currently in place in the UK to offer catch-up vaccination to migrants on arrival and the need for health-care provider skills and knowledge of catch-up vaccination to be improved. Focus group discussions and interviews with practice staff (n = 32) identified limited appointment/follow-up time, staff knowledge gaps, inadequate engagement routes, and low incentivisation as challenges that will need to be addressed. However, they underscored the potential of staff champions, trust-building mechanisms, and community-based approaches to strengthen catch-up vaccination uptake among migrants.ConclusionsGiven the significant catch-up vaccination needs of migrants in our sample, and the current barriers to driving uptake identified, our findings suggest it will be important to explore this public health issue further, potentially through a larger study or trial. Strengthening existing pathways, staff capacity and knowledge in primary care, alongside implementing new strategies centred on cultural competence and building trust with migrant communities will be important focus areas.

Safety and immunogenicity of a DNA vaccine with subtype C gp120 protein adjuvanted with MF59® or AS01B: a phase 1/2a HIV-1 vaccine trial

Despite progress in HIV prevention and treatment, an estimated 1.3 million people were newly infected with HIV in 2022,1 highlighting the urgent need for an effective vaccine. To date, the RV144 trial remains the only HIV vaccine trial that has demonstrated partial efficacy against acquisition.2 The Pox-Protein Public-Private Partnership (P5) was established with the aims of improving on RV144 by developing a vaccine capable of protecting against a broader diversity of HIV strains and achieving a better understanding of immune responses associated with preventing HIV infection.3 Vaccine concepts in the P5 program have focused on clade C immunogens, targeting predominant strains of East and Southern Africa, where approximately half of the 39 million people living with HIV reside.1 The RV144 regimen, originally designed to protect against subtype B/E strains, was adapted to incorporate clade C antigens and adjuvanted with MF59®.4 This regimen demonstrated adequate immunogenicity in the HVTN100 phase 1/2a trial,5 and was further evaluated in the HVTN702 efficacy trial in South Africa, but ultimately discontinued due to non-efficacy.6 In parallel, the P5 designed the correlates program: a series of phase 1/2a trials to evaluate vaccine candidates based on favorable immune profiles of putative correlates of protection. These trials employed novel prime-boost and co-administration regimens, varied protein doses, and used new adjuvants and vaccine delivery systems, with an emphasis on shared immunological endpoints to allow for cross-study comparisons. Preclinical studies have shown promising immune responses using DNA/protein combination vaccines.7,8 A comparison of responses between HVTN100 (ALVAC) and HVTN111 (DNA) trials indicated that DNA priming with a protein boost led to increased antibody and cellular responses compared to priming with the canarypox vector.9 In the HVTN105 trial, both a DNA prime-protein boost and a co-administration regimen induced potent and durable V1/V2 binding antibody responses (a known correlate of lower HIV-1 infection risk in RV144), with co-administration inducing early antibody responses.10 Furthermore, in the HVTN096 trial, including gp120 Env protein at the priming stage, co-administered with either NYVAC or DNA, elicited earlier and even greater antibody responses.11 The adjuvant system 01 (AS01) has been successfully tested in vaccine trials for other infectious diseases including malaria,12 shingles,13,14 and tuberculosis.15 Some HIV vaccine studies have also used AS01 and have shown that it contributes to the induction of robust and persistent cellular and humoral responses.16,17 MF59® has likewise been used in several licensed vaccines and pre-clinical studies,18 inducing strong and durable T-cell memory and humoral responses. MF59® was also used in HVTN studies with ALVAC 5 and was therefore chosen for comparison with AS01B in this trial. Thus, the aim of the HVTN108 trial was to evaluate the safety and immunogenicity of the DNA vaccine with different HIV clade C protein doses, adjuvanted with MF59® or AS01B, and dosed in prime-boost or co-administration regimens.

Alginate functionalized chitosan nanoparticles using multilayer co-axial electro-spraying for ovalbumin controlled release via oral delivery

The current oral vaccine delivery presents numerous challenges due to physiological barriers in the gastrointestinal tract including antigen degradation by enzymes and gastric pH conditions. Contributing to overcome these problems, this work developed non-cross-linked chitosan (CHI) nanoparticles, with/without functionalization with alginate (ALG), using multilayer co-axial electro-spraying method, to orally deliver ovalbumin (OVA), a model antigen. The prepared OVA@CHI and OVA@CHI@ALG nanoparticles possessed spherical shape, uniform size and non-agglomeration, high OVA encapsulation efficiency of above 90 %, and core-shell structure with mean diameters of 276.9 ± 70.7 nm (for OVA@CHI) and 304.3 ± 63.9 nm (for OVA@CHI@ALG), determined via SEM images. The particle hydrodynamic diameters, analyzed by the DLS method, were 313.0 ± 72.4 nm for OVA@CHI and 367.6 ± 83.2 nm for OVA@CHI@ALG, in agreement with the SEM results. Additionally, the material functional group interactions and the polyelectrolyte complex formations were confirmed by FTIR spectra and TGA/DSC thermo-grams, indicating the successful formulation. Subsequently, the OVA@CHI@ALG nanoparticles revealed good stability in acidic environment under the presence of digestive enzymes. The OVA release profiles of OVA@CHI@ALG nanoparticles exhibited limited release in simulated gastric fluid (pH 1.2), followed by sustained release in simulated intestinal fluid (pH 6.8) and simulated colonic fluid (pH 7.4) over a 48-h test period. Interestingly, the primary structure of OVA, analyzed by SDS-PAGE analysis, was maintained during the preparation process and after the release test, while the OVA secondary structure, examined by circular dichroism measurement, demonstrated a decrease of α-helix and an increase of β-sheet contents. Finally, the in vitro mucin-binding study indicated a significant adhesive efficiency of 69.21 ± 4.24 % for OVA@CHI and 75.07 ± 2.58 % for OVA@CHI@ALG at pH 7.4. Conclusively, the OVA@CHI@ALG nanoparticles fabricated by tri-axial electro-spraying method could be a promising oral vaccine delivery system for sustained release of OVA.

Media Discourse Regarding COVID-19 Vaccinations for Children Aged 5 to 11 Years in Australia, Canada, the United Kingdom, and the United States: Comparative Analysis Using the Narrative Policy Framework.

Media narratives can shape public opinion and actions, influencing the uptake of pediatric COVID-19 vaccines. The COVID-19 pandemic has occurred at a time where infodemics, misinformation, and disinformation are present, impacting the COVID-19 response. This study aims to investigate how narratives about pediatric COVID-19 vaccines in the media of 4 English-speaking countries: the United States, Australia, Canada, and the United Kingdom. The Narrative Policy Framework was used to guide the comparative analyses of the major print and web-based news agencies' media regarding COVID-19 vaccines for children aged 5 to 11 years. Data were sought using systematic searching on Factiva (Dow Jones) of 4 key phases of pediatric vaccine approval and rollout. A total of 400 articles (n=287, 71.8% in the United States, n=40, 10% in Australia, n=60, 15% in Canada, and n=13, 3% in the United Kingdom) met the search criteria and were included. Using the Narrative Policy Framework, the following were identified in each article: hero, villain, survivor, and plot. The United States was the earliest country to vaccinate children, and other countries' media often lauded the United States for this. Australian and Canadian media narratives about vaccines for children aged 5 to 11 years were commonly about protecting susceptible people in society, whereas the US and the UK narratives focused more on the vaccine helping children return to school. All 4 countries focused on the vaccines for children aged 5 to 11 years as being key to "ending" the pandemic. Australian and Canadian narratives frequently compared vaccine rollouts across states or provinces and bemoaned local progress in vaccine delivery compared with other countries globally. Canadian and US narratives highlighted the "infodemic" about the COVID-19 pandemic and disinformation regarding child vaccines as impeding uptake. All 4 countries-the United States, Australia, the United Kingdom, and Canada-used war imagery in reporting about COVID-19 vaccines for children. The advent of the Omicron variant demonstrated that populations were fatigued by the COVID-19 pandemic, and the media reporting increasingly blamed the unvaccinated. The UK media narrative was unique in describing vaccinating children as a distraction from adult COVID-19 vaccination efforts. The United States and Canada had narratives expressing anger about potential vaccine passports for children. In Australia, general practitioners were labelled as heroes. Finally, the Canadian narrative suggested altruistic forgoing of COVID-19 vaccine "boosters" as well as pediatric COVID-19 vaccines to benefit those in poorer nations. Public health emergencies require clear; compelling and accurate communication. The stories told during this pandemic are compelling because they contain the classic elements of a narrative; however, they can be reductive and inaccurate.

Research Progress on Liposome Pulmonary Delivery of Mycobacterium tuberculosis Nucleic Acid Vaccine and Its Mechanism of Action.

Traditional vaccines have played an important role in the prevention and treatment of infectious diseases, but they still have problems such as low immunogenicity, poor stability, and difficulty in inducing lasting immune responses. In recent years, the nucleic acid vaccine has emerged as a relatively cheap and safe new vaccine. Compared with traditional vaccines, nucleic acid vaccine has some unique advantages, such as easy production and storage, scalability, and consistency between batches. However, the direct administration of naked nucleic acid vaccine is not ideal, and safer and more effective vaccine delivery systems are needed. With the rapid development of nanocarrier technology, the combination of gene therapy and nanodelivery systems has broadened the therapeutic application of molecular biology and the medical application of biological nanomaterials. Nanoparticles can be used as potential drug-delivery vehicles for the treatment of hereditary and infectious diseases. In addition, due to the advantages of lung immunity, such as rapid onset of action, good efficacy, and reduced adverse reactions, pulmonary delivery of nucleic acid vaccine has become a hot spot in the field of research. In recent years, lipid nanocarriers have become safe, efficient, and ideal materials for vaccine delivery due to their unique physical and chemical properties, which can effectively reduce the toxic side effects of drugs and achieve the effect of slow release and controlled release, and there have been a large number of studies using lipid nanocarriers to efficiently deliver target components into the body. Based on the delivery of tuberculosis (TB) nucleic acid vaccine by lipid carrier, this article systematically reviews the advantages and mechanism of liposomes as a nucleic acid vaccine delivery carrier, so as to lay a solid foundation for the faster and more effective development of new anti-TB vaccine delivery systems in the future.

Modelling COVID-19 Vaccination in the UK: Impact of the Autumn 2022 and Spring 2023 Booster Campaigns.

The delivery of COVID-19 vaccines was successful in reducing hospitalizations and mortality. However, emergence of the Omicron variant resulted in increased virus transmissibility. Consequently, booster vaccination programs were initiated to decrease the risk of severe disease and death among vulnerable members of the population. This study aimed to estimate the effects of the booster program and alternative vaccination strategies on morbidity and mortality due to COVID-19 in the UK. A Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to assess the impact of several vaccination strategies on severe outcomes associated with COVID-19, including hospitalizations, mortality, National Health Service (NHS) capacity quantified by hospital general ward and intensive care unit (ICU) bed days, and patient productivity. The model accounted for age-, risk- and immunity-based stratification of the UK population. Outcomes were evaluated over a 48-week time horizon from September 2022 to August 2023 considering the actual UK autumn 2022/spring 2023 booster campaigns and six counterfactual strategies. The model estimated that the autumn 2022/spring 2023 booster campaign resulted in a reduction of 18,921hospitalizations and 1463 deaths, compared with a no booster scenario. Utilization of hospital bed days due to COVID-19 decreased after the autumn 2022/spring 2023 booster campaign. Expanding the booster eligibility criteria and improving uptake improved all outcomes, including averting twice as many ICU admissions, preventing more than 20% additional deaths, and a sevenfold reduction in long COVID, compared with the autumn 2022/spring 2023 booster campaign. The number of productive days lost was reduced by fivefold indicating that vaccinating a wider population has a beneficial impact on the morbidities associated with COVID-19. Our modelling demonstrates that the autumn 2022/spring 2023 booster campaign reduced COVID-19-associated morbidity and mortality. Booster campaigns with alternative eligibility criteria warrant consideration in the UK, given their potential to further reduce morbidity and mortality as future variants emerge.

Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis.

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.

Microneedle patch with pure drug tips for delivery of liraglutide: pharmacokinetics in rats and minipigs.

Transdermal delivery of peptide drugs is almost impossible with conventional penetration enhancers because of epidermal barrier function. Microneedle (MN) patches can bypass the epidermal barrier and have been developed for trans- and intradermal delivery of peptide drugs and vaccines. However, dissolving MN patches are limited by low drug loading capacities due to their small size and admixture of drug and water-soluble excipients. Furthermore, few in vivo pharmacokinetic studies, especially in large animals such as pigs, have been performed to assess post-application systemic drug exposure. Here, we developed a dissolving MN patch with pure liraglutide at the needle tips. The MN patch could load up to 2.21 ± 0.14mg of liraglutide in a patch size of 0.9 cm2, which was nearly two orders of magnitude higher than that obtained with conventional MN patches of the same size. Raman imaging confirmed that liraglutide was localized at the MN tips. The MN had sufficient mechanical strength to penetrate the epidermis and could deliver up to 0.93 ± 0.04mg of liraglutide into skin with a dosing variability of less than 6.8%. The MN patch delivery enabled faster absorption of liraglutide than that provided by subcutaneous (S.C.) injection, and achieved relative bioavailability of 69.8% and 46.3% compared to S.C. injection in rats and minipigs, respectively. The MN patch also exhibited similar patterns of anti-hyperglycemic effect in diabetic rats and individual variability in pharmacokinetic parameters as S.C. injection. The liraglutide MN application was well tolerated; no skin irritation was observed in minipigs except for mild erythema occurring within 4h after once daily administration for 7days at the same site. Our preclinical study suggests that MN patch with pure drug needle tips might offer a safe and effective alternative to S.C. injection for administration of liraglutide.

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria.

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

Mammalian Cell Membrane Hybrid Polymersomes for mRNA Delivery.

Cell membranes are structures essential to the cell function and adaptation. Recent studies have targeted cell membranes to identify their protective and interactive properties. Leveraging these attributes of cellular membranes and their application to vaccine delivery is gaining increasing prominence. This study aimed to fuse synthetic polymeric nanoparticles with cell membranes to develop cell membrane hybrid polymersomes (HyPSomes) for enhanced vaccine delivery. We designed a platform to hybridize cell membranes with methoxy-poly(ethylene glycol)-block-polylactic acid nanoparticles by using the properties of both components. The formed HyPSomes were optimized by using dynamic light scattering, transmission electron microscopy, and Förster resonance energy transfer, and their stability was confirmed. The synthesized HyPSomes replicated the antigenic surface of the source cells and possessed the stability and efficacy of synthetic nanoparticles. These HyPSomes demonstrated enhanced cellular uptake and translation efficiency and facilitated endosome escape. HyPSomes showed outstanding capabilities for the delivery of foreign mRNAs to antigen-presenting cells. HyPSomes may serve as vaccine delivery systems by bridging the gap between synthetic and natural systems. These systems could be used in other contexts, e.g., diagnostics and drug delivery.

Nanosafety: a Perspective on Nano-Bio Interactions.

Engineered nanomaterials offer numerous benefits to society ranging from environmental remediation to biomedical applications such as drug or vaccine delivery as well as clean and cost-effective energy production and storage, and the promise of a more sustainable way of life. However, as nanomaterials of increasing sophistication enter the market, close attention to potential adverse effects on human health and the environment is needed. Here a critical perspective on nanotoxicological research is provided; the authors argue that it is time to leverage the knowledge regarding the biological interactions of nanomaterials to achieve a more comprehensive understanding of the human health and environmental impacts of these materials. Moreover, it is posited that nanomaterials behave like biological entities and that they should be regulated as such.