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Expert Opinion on Drug Delivery Oct 2021: The oral route of vaccination is pain- and needle-free and can induce systemic and mucosal immunity. However, gastrointestinal barriers and antigen degradation impose... (Review)
Review
: The oral route of vaccination is pain- and needle-free and can induce systemic and mucosal immunity. However, gastrointestinal barriers and antigen degradation impose significant hurdles in the development of oral vaccines. Live attenuated viruses and bacteria can overcome these barriers but at the risk of introducing safety concerns. As an alternative, particles have been investigated for antigen protection and delivery, yet there are no FDA-approved oral vaccines based on particle-based delivery systems. Our objective was to discover underlying determinants that can explain the current inadequacies and identify paradigms that can be implemented in future for successful development of oral vaccines relying on particle-based delivery systems.: We reviewed literature related to the use of particles for oral vaccination and placed special emphasis on formulation characteristics and administration schedules to gain an insight into how these parameters impact production of antigen-specific antibodies in systemic and mucosal compartments.: Despite the long history of vaccines, particle-based oral vaccination is a relative new field with the first study published in 1989. Substantial variability exists between different studies with respect to dosing schedules, number of doses, and the amount of vaccine per dose. Most studies have not used adjuvants in the formulations. Better standardization in vaccination parameters is required to improve comparison between experiments, and adjuvants should be used to enhance the systemic and mucosal immune responses and to reduce the number of doses, which will make oral vaccines more attractive.
Topics: Adjuvants, Immunologic; Drug Delivery Systems; Immunity, Mucosal; Vaccination; Vaccines
PubMed: 34148474
DOI: 10.1080/17425247.2021.1946511 -
Cells Nov 2020Atherosclerosis is the major underlying pathology of cardiovascular diseases that together are the leading cause of death worldwide. The formation of atherosclerotic... (Review)
Review
Atherosclerosis is the major underlying pathology of cardiovascular diseases that together are the leading cause of death worldwide. The formation of atherosclerotic plaques is driven by chronic vascular inflammation. Although several risk factors have been identified and significant progress in disease prevention and treatment has been made, no therapeutic agents targeting inflammation are clinically available. Recent clinical trials established the potential of anti-inflammatory therapies as a treatment of atherosclerosis. However, adverse impacts on host defense have raised safety concerns about these therapies. Scientific evidence during the past 40 years implicated an adaptive immune response against plaque-associated autoantigens in atherogenesis. Preclinical data have underscored the protective potential of immunization against such targets precisely and without the impairment of host defense. In this review, we discuss the current vaccination strategies against atherosclerosis, supposed mechanisms of action, therapeutic potential, and the challenges that must be overcome in translating this idea into clinical practice.
Topics: Adaptive Immunity; Animals; Atherosclerosis; Autoantigens; Humans; Inflammation; Plaque, Atherosclerotic; Vaccination; Vaccines
PubMed: 33266027
DOI: 10.3390/cells9122560 -
The Journal of Allergy and Clinical... Jul 2022Recent events involving the global coronavirus pandemic have focused attention on vaccination strategies. Although tremendous advances have been made in subcutaneous and... (Review)
Review
Recent events involving the global coronavirus pandemic have focused attention on vaccination strategies. Although tremendous advances have been made in subcutaneous and intramuscular vaccines during this time, one area that has lagged in implementation is mucosal immunization. Mucosal immunization provides several potential advantages over subcutaneous and intramuscular routes, including protection from localized infection at the site of entry, clearance of organisms on mucosal surfaces, induction of long-term immunity through establishment of central and tissue-resident memory cells, and the ability to shape regulatory responses. Despite these advantages, significant barriers remain to achieving effective mucosal immunization. The epithelium itself provides many obstacles to immunization, and the activation of immune recognition and effector pathways that leads to mucosal immunity has been difficult to achieve. This review will highlight the potential advantages of mucosal immunity, define the barriers to mucosal immunization, examine the immune mechanisms that need to be activated on mucosal surfaces, and finally address recent developments in methods for mucosal vaccination that have shown promise in generating immunity on mucosal surfaces in human trials.
Topics: Humans; Immunity, Mucosal; Immunization; Mucous Membrane; Vaccination; Vaccines
PubMed: 35569567
DOI: 10.1016/j.jaci.2022.05.002 -
Nature Immunology Dec 2022Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms...
Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination.
Topics: Humans; Antibody Formation; Vaccination; Vaccines; Adjuvants, Immunologic; Immunity, Innate
PubMed: 36316476
DOI: 10.1038/s41590-022-01329-5 -
Clinical Microbiology Reviews Jun 2023Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to... (Review)
Review
Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.
Topics: Humans; Clostridioides difficile; Immunity, Innate; Vaccination; Clostridium Infections
PubMed: 37162338
DOI: 10.1128/cmr.00157-22 -
Proceedings of the National Academy of... Aug 2014Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and... (Review)
Review
Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.
Topics: Communicable Disease Control; Cost-Benefit Analysis; Evidence-Based Medicine; Humans; Immunity, Herd; Socioeconomic Factors; Vaccination
PubMed: 25136129
DOI: 10.1073/pnas.1400475111 -
Advanced Drug Delivery Reviews Nov 2021Recent estimates suggest that one in two sexually active individuals will acquire a sexually transmitted infection by age 25, an alarming statistic that amounts to over... (Review)
Review
Recent estimates suggest that one in two sexually active individuals will acquire a sexually transmitted infection by age 25, an alarming statistic that amounts to over 1 million new infections per day worldwide. Vaccination against STIs is highly desirable for alleviating this global burden of disease. Vaginal immunization is a promising strategy to combat transmission via the vaginal mucosa. The vagina is typically considered a poor inductive site for common correlates of adaptive immunity. However, emerging evidence suggests that immune tolerance may be overcome by precisely engineered vaccination schemes that orchestrate cell-mediated immunity and establish tissue resident memory immune cells. In this review, we will discuss the unique immunological milieu of the vaginal mucosa and our current understanding of correlates of pathogenesis and protection for several common STIs. We then present a summary of recent vaginal vaccine studies and explore the role that mucosal adjuvants and delivery systems play in enhancing protection according to requisite features of immunity. Finally, we offer perspectives on the challenges and future directions of vaginal vaccine delivery, discussing remaining physiological barriers and innovative vaccine formulations that may overcome them.
Topics: Adaptive Immunity; Female; Humans; Immune Tolerance; Vaccination; Vaccines; Vagina
PubMed: 34481031
DOI: 10.1016/j.addr.2021.113956 -
Current Opinion in Immunology Oct 2023Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues,... (Review)
Review
Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues, including oral, nasal, pulmonary, intestinal, and urogenital surfaces. Mucosal vaccines not only induce local immune effector elements, such as secretory Immunoglobulin A (IgA) reaching the luminal site of the mucosa, but also systemic immunity. Moreover, mucosal vaccines may trigger immunity in distant mucosal tissues because of the homing of primed antigen-specific immune cells toward local and distant mucosal tissue via the common mucosal immune system. While most licensed intramuscular vaccines induce only systemic immunity, next-generation mucosal vaccines may outperform parenteral vaccination strategies by also eliciting protective mucosal immune responses that block infection and/or transmission. Especially the nasal route of vaccination, targeting the nasal-associated lymphoid tissue, is attractive for local and distant mucosal immunization. In numerous studies, bacterial outer membrane vesicles (OMVs) have proved attractive as vaccine platform for homologous bacterial strains, but also as antigen delivery platform for heterologous antigens of nonbacterial diseases, including viruses, parasites, and cancer. Their application has also been extended to mucosal delivery. Here, we will summarize the characteristics and clinical potential of (engineered) OMVs as vaccine platform for mucosal, especially intranasal delivery.
Topics: Humans; Vaccines; Administration, Intranasal; Immunization; Vaccination; Immunity, Mucosal; Mucous Membrane
PubMed: 37598549
DOI: 10.1016/j.coi.2023.102376 -
Nanoscale Jan 2022Mucosal vaccination can elicit both systemic and mucosal immunity, and therefore has the potential to not only treat mucosal immune diseases, prevent the pathogen... (Review)
Review
Mucosal vaccination can elicit both systemic and mucosal immunity, and therefore has the potential to not only treat mucosal immune diseases, prevent the pathogen infection at the mucosal entry sites, but also treat distant or systemic immune disorders. However, only a few mucosal vaccines have been approved for human use in the clinic. Effective mucosal immunization requires the delivery of immunogenic agents to appropriate mucosal surfaces, which remains significantly challenging due to the essential biological barriers presenting at mucosal tissues. In the past decade, remarkable progress has been made in the development of pulmonary mucosal nanovaccines. The nanovaccines leverage advanced nanoparticle-based pulmonary delivery technologies on the characteristics of large surface area and rich antigen presentation cell environment of the lungs for triggering robust immune protection against various mucosal diseases. Herein, we review current methods and formulations of pulmonary delivery, discuss the design strategies of mucosal nanovaccines for potent and long-lasting immune responses, and highlight recent advances in the application of lipid-based pulmonary nanovaccines against mucosal diseases. These advances promise to accelerate the development of novel mucosal nanovaccines for the prophylaxis and therapy of infectious diseases, and cancer, as well as autoimmune disorders at mucosal tissues.
Topics: Humans; Immunity, Mucosal; Lung; Mucous Membrane; Vaccination; Vaccines
PubMed: 34918733
DOI: 10.1039/d1nr06512b -
Vaccine Dec 2018eHealth interventions may help increase vaccination uptake and health literacy related to immunization and improve immunization program efficiency. (Review)
Review
BACKGROUND
eHealth interventions may help increase vaccination uptake and health literacy related to immunization and improve immunization program efficiency.
OBJECTIVES
To see where and how eHealth technologies have had a positive impact on immunization practices-using eHealth strategies to increase vaccination uptake, improve immunization program efficiency and advance heath literacy related to immunizations.
METHODS
An overview of systematic reviews was conducted, searching PubMed, Scopus, Embase, and Web of Science for systematic reviews published through August 2017 for eHealth and immunizations (using pre-determined concepts for each). Two independent reviewers selected studies based on a priori criteria; disagreement was resolved by consensus. The quality of the included studies was evaluated using the Measurement Tool to Assess Systematic Reviews (AMSTAR).
RESULTS
The primary search identified 198 results. After eliminating duplicates 158 remained. Upon applying the a priori set criteria to these, six articles were left to analyze. Four articles showed a positive relationship (a demonstrated benefit, improvement, increase in vaccination uptake, etc. when using eHealth technologies for immunization), one showed a promising relation / with potential, and one showed unknown effects as it focused on the difficulty of analyzing cost-benefits of immunization information systems (IIS).
CONCLUSION
The review leads to a recommendation of using eHealth technologies to encourage immunizations and increase vaccination adherence and uptake and to continue assessing and documenting the use of eHealth for immunization.
Topics: Cost-Benefit Analysis; Efficiency, Organizational; Humans; Immunization Programs; Systematic Reviews as Topic; Telemedicine; Vaccination Coverage
PubMed: 29983255
DOI: 10.1016/j.vaccine.2018.06.076