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Human Vaccines & Immunotherapeutics Dec 2024Cancer immunotherapy has emerged as a promising strategy to treat cancer patients. Among the wide range of immunological approaches, cancer vaccines have been... (Review)
Review
Cancer immunotherapy has emerged as a promising strategy to treat cancer patients. Among the wide range of immunological approaches, cancer vaccines have been investigated to activate and expand tumor-reactive T cells. However, most cancer vaccines have not shown significant clinical benefit as monotherapies. This is likely due to the antigen targets of vaccines, "self" proteins to which there is tolerance, as well as to the immunosuppressive tumor microenvironment. To help circumvent immune tolerance and generate effective immune responses, adjuvants for cancer vaccines are necessary. One representative adjuvant family is Toll-Like receptor (TLR) agonists, synthetic molecules that stimulate TLRs. TLRs are the largest family of pattern recognition receptors (PRRs) that serve as the sensors of pathogens or cellular damage. They recognize conserved foreign molecules from pathogens or internal molecules from cellular damage and propel innate immune responses. When used with vaccines, activation of TLRs signals an innate damage response that can facilitate the development of a strong adaptive immune response against the target antigen. The ability of TLR agonists to modulate innate immune responses has positioned them to serve as adjuvants for vaccines targeting infectious diseases and cancers. This review provides a summary of various TLRs, including their expression patterns, their functions in the immune system, as well as their ligands and synthetic molecules developed as TLR agonists. In addition, it presents a comprehensive overview of recent strategies employing different TLR agonists as adjuvants in cancer vaccine development, both in pre-clinical models and ongoing clinical trials.
Topics: Humans; Adjuvants, Vaccine; Toll-Like Receptor Agonists; Cancer Vaccines; Adjuvants, Immunologic; Antigens; Neoplasms; Tumor Microenvironment
PubMed: 38155525
DOI: 10.1080/21645515.2023.2297453 -
International Journal of Molecular... Aug 2023Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea... (Review)
Review
Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea creatures. They consist of a hydrophilic sugar moiety linked to a lipophilic aglycone, resulting in an amphiphilic nature and unique functional properties. Their amphiphilic structures enable saponins to exhibit surface-active properties, resulting in stable foams and complexes with various molecules. In the context of food applications, saponins are utilized as natural emulsifiers, foaming agents, and stabilizers. They contribute to texture and stability in food products and have potential health benefits, including cholesterol-lowering and anticancer effects. Saponins possess additional bioactivities that make them valuable in the pharmaceutical industry as anti-inflammatory, antimicrobial, antiviral, and antiparasitic agents to name a few. Saponins can demonstrate cytotoxic activity against cancer cell lines and can also act as adjuvants, enhancing the immune response to vaccines. Their ability to form stable complexes with drugs further expands their potential in drug delivery systems. However, challenges such as bitterness, cytotoxicity, and instability under certain conditions need to be addressed for effective utilization of saponins in foods and related applications. In this paper, we have reviewed the chemistry, functionality, and application aspects of saponins from various plant sources, and have summarized the regulatory aspects of the food-based application of quillaja saponins. Further research to explore the full potential of saponins in improving food quality and human health has been suggested. It is expected that this article will be a useful resource for researchers in food, feed, pharmaceuticals, and material science.
Topics: Humans; Saponins; Food; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antiparasitic Agents
PubMed: 37686341
DOI: 10.3390/ijms241713538 -
Frontiers in Immunology 2023SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early T cell-driven immunity leads to... (Review)
Review
SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early T cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation and imbalanced humoral response. Analyses of acute SARS-CoV-2 infection have revealed that mild COVID-19 course is characterized by an early induction of specific T cells within the first 7 days of symptoms, coordinately followed by antibody production for an effective control of viral infection. In contrast, patients who do not develop an early specific cellular response and initiate a humoral immune response with subsequent production of high levels of antibodies, develop severe symptoms. Yet, delayed and persistent bystander CD8+ T cell activation has been also reported in hospitalized patients and could be a driver of lung pathology. Literature supports that long-term maintenance of T cell response appears more stable than antibody titters. Up to date, virus-specific T cell memory has been detected 22 months post-symptom onset, with a predominant IL-2 memory response compared to IFN-γ. Furthermore, T cell responses are conserved against the emerging variants of concern (VoCs) while these variants are mostly able to evade humoral responses. This could be partly explained by the high HLA polymorphism whereby the viral epitope repertoire recognized could differ among individuals, greatly decreasing the likelihood of immune escape. Current COVID-19-vaccination has been shown to elicit Th1-driven spike-specific T cell response, as does natural infection, which provides substantial protection against severe COVID-19 and death. In addition, mucosal vaccination has been reported to induce strong adaptive responses both locally and systemically and to protect against VoCs in animal models. The optimization of vaccine formulations by including a variety of viral regions, innovative adjuvants or diverse administration routes could result in a desirable enhanced cellular response and memory, and help to prevent breakthrough infections. In summary, the increasing evidence highlights the relevance of monitoring SARS-CoV-2-specific cellular immune response, and not only antibody levels, as a correlate for protection after infection and/or vaccination. Moreover, it may help to better identify target populations that could benefit most from booster doses and to personalize vaccination strategies.
Topics: Animals; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antibodies; CD8-Positive T-Lymphocytes; COVID-19; SARS-CoV-2; Humans
PubMed: 36776863
DOI: 10.3389/fimmu.2023.1107803 -
Phytotherapy Research : PTR Dec 2022The COVID-19 pandemic is shaking up global scientific structures toward addressing antibiotic resistance threats and indicates an urgent need to develop more... (Review)
Review
The COVID-19 pandemic is shaking up global scientific structures toward addressing antibiotic resistance threats and indicates an urgent need to develop more cost-effective vaccines. Vaccine adjuvants play a crucial role in boosting immunogenicity and improving vaccine efficacy. The toxicity and adversity of most adjuvant formulations are the major human immunization problems, especially in routine pediatric and immunocompromised patients. The present review focused on preclinical studies of immunoadjuvant plant proteins in use with antiparasitic, antifungal, and antiviral vaccines. Moreover, this report outlines the current perspective of immunostimulant plant protein candidates that can be used by researchers in developing new generations of vaccine-adjuvants. Future clinical studies are required to substantiate the plant proteins' safety and applicability as a vaccine adjuvant in pharmaceutical manufacturing.
Topics: Humans; Adjuvants, Immunologic; Adjuvants, Vaccine; Plant Proteins; Vaccines
PubMed: 36128599
DOI: 10.1002/ptr.7624 -
Cells Aug 2023Treatment for the deadly brain tumor glioblastoma (GBM) has been improved through the non-invasive addition of alternating electric fields, called tumor treating fields...
Treatment for the deadly brain tumor glioblastoma (GBM) has been improved through the non-invasive addition of alternating electric fields, called tumor treating fields (TTFields). Improving both progression-free and overall survival, TTFields are currently approved for treatment of recurrent GBMs as a monotherapy and in the adjuvant setting alongside TMZ for newly diagnosed GBMs. These TTFields are known to inhibit mitosis, but the full molecular impact of TTFields remains undetermined. Therefore, we sought to understand the ability of TTFields to disrupt the growth patterns of and induce kinomic landscape shifts in TMZ-sensitive and -resistant GBM cells. We determined that TTFields significantly decreased the growth of TMZ-sensitive and -resistant cells. Kinomic profiling predicted kinases that were induced or repressed by TTFields, suggesting possible therapy-specific vulnerabilities. Serving as a potential pro-survival mechanism for TTFields, kinomics predicted the increased activity of platelet-derived growth-factor receptor alpha (PDGFRα). We demonstrated that the addition of the PDGFR inhibitor, crenolanib, to TTFields further reduced cell growth in comparison to either treatment alone. Collectively, our data suggest the efficacy of TTFields in vitro and identify common signaling responses to TTFields in TMZ-sensitive and -resistant populations, which may support more personalized medicine approaches.
Topics: Humans; Glioblastoma; Brain Neoplasms; Precision Medicine; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37681903
DOI: 10.3390/cells12172171 -
Analytical Cellular Pathology... 2020Metformin has been used for a long time as an antidiabetic medication for type 2 diabetes. It is used either as a monotherapy or in combination with other antidiabetic... (Review)
Review
Metformin has been used for a long time as an antidiabetic medication for type 2 diabetes. It is used either as a monotherapy or in combination with other antidiabetic medications. The drug came into prominence in diabetes and other conditions with cardiovascular risk after the landmark study of 1995 by the United Kingdom Prospective Diabetes Study which emphasized its importance. However, the drug has been used in experimental trials in various aspects of medicine and pharmacology such as in reproductive medicine, cancer chemotherapy, metabolic diseases, and neurodegenerative diseases. It has been in use in the treatment of polycystic ovarian disease and obesity and is being considered in type 1 diabetes. This study seeks to evaluate the relevance of metformin in cancer management. Different mechanisms have been proposed for its antitumor action which involves the following: (a) the activation of adenosine monophosphate kinase, (b) modulation of adenosine A1 receptor (ADORA), (c) reduction in insulin/insulin growth factors, and (d) the role of metformin in the inhibition of endogenous reactive oxygen species (ROS); and its resultant damage to deoxyribonucleic acid (DNA) molecule is another paramount antitumor mechanism.
Topics: Adjuvants, Pharmaceutic; Animals; Carcinogens; Clinical Trials as Topic; Humans; Metformin; Neoplasms; Treatment Outcome
PubMed: 32399389
DOI: 10.1155/2020/7180923 -
Microbial Biotechnology Jul 2023Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health.... (Review)
Review
Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.
Topics: Drug Resistance, Multiple, Bacterial; Staphylococcus aureus; Antimicrobial Cationic Peptides; Biological Products; Anti-Bacterial Agents; Adjuvants, Pharmaceutic; Drug Synergism; Immunoconjugates; Phage Therapy; Drug Development; Staphylococcal Infections; Humans
PubMed: 37178319
DOI: 10.1111/1751-7915.14268 -
Ecotoxicology and Environmental Safety Dec 2021Natural adjuvants are novel options to reduce the doses of chemical herbicides. The aim of the current study was to examine the compositions and adjuvant effects of...
Natural adjuvants are novel options to reduce the doses of chemical herbicides. The aim of the current study was to examine the compositions and adjuvant effects of rosin and coconut oil on herbicides using a combination of indoor experiment and field trial. The GC-MS results showed that the main component of rosin was abietic acid (40.02%), and the main components of coconut oil were 2-pentanone, 4-hydroxy-4-methyl- (21.45%) and dodecanoic acid (14.59%). In greenhouse experiment, rosin showed a significant adjuvant effect on nicosulfuron against Digitaria sanguinalis and Amaranthus retroflexus, with the GR ratios of 1.47 and 1.69, respectively. The GR values of nicosulfuron in the present of coconut oil were 3.99 and 10.13 g a.i./hm against D. sanguinalis and A. retroflexus, lower than that of individual application. The adjuvant effect of rosin and coconut oil on mesotrione was also found. In field trial, the fresh weight control efficiency of nicosulfuron (45 g a.i./hm) and mesotrione (112.5 g a.i./hm) was significantly improved after the addition of rosin and coconut oil, similar with that of recommended dose. Rosin and coconut oil could reduce the contact angle of nicosulfuron, with the results of 56.68° and 53.90°, respectively, lower than that of individual application. Furthermore, rosin and coconut oil could decrease the surface tension, wetting and penetration time; and increase the spreading diameter and maximum retention. Both rosin and coconut oil have adjuvant effects on herbicides in the lab & field with multiple mechanisms. Thus, they have the potential to be developed into natural adjuvants for herbicide formulation to control weeds.
Topics: Adjuvants, Pharmaceutic; Coconut Oil; Cyclohexanones; Pyridines; Resins, Plant; Sulfonylurea Compounds
PubMed: 34509967
DOI: 10.1016/j.ecoenv.2021.112766 -
The Lancet. Infectious Diseases Oct 2023Lyme borreliosis, potentially associated with serious long-term complications, is caused by the species complex Borrelia burgdorferi sensu lato. We investigated a novel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Lyme borreliosis, potentially associated with serious long-term complications, is caused by the species complex Borrelia burgdorferi sensu lato. We investigated a novel Lyme borreliosis vaccine candidate (VLA15) targeting the six most common outer surface protein A (OspA) serotypes 1-6 to prevent infection with pathogenic Borrelia spp prevalent in Europe and North America.
METHODS
This was a partially randomised, observer-masked, phase 1 study in healthy adults older than 18 years to younger than 40 years (n=179) done in trial sites in Belgium and the USA. Following a non-randomised run-in phase, a sealed envelope randomisation method was applied with a 1:1:1:1:1:1 ratio; three dose concentrations of VLA15 (12 μg, 48 μg, and 90 μg) were administered by intramuscular injection on days 1, 29, and 57. The primary outcome was safety (frequency of adverse events up to day 85) assessed in participants who received at least one vaccination. Immunogenicity was a secondary outcome. The trial is registered with ClinicalTrials.gov, NCT03010228, and is complete.
FINDINGS
Between Jan 23, 2017 and Jan 16, 2019, of 254 participants screened for eligibility, 179 were randomly assigned into six groups: alum-adjuvanted 12 μg (n=29), 48 μg (n=31), or 90 μg (n=31) and non-adjuvanted 12 μg (n=29 participants), 48 μg (n=29), or 90 μg (n=30). VLA15 was safe and well tolerated and the majority of adverse events were mild or moderate. Overall, adverse events were more frequent in the 48 μg and 90 μg groups (range 28-30 participants [94-97%]) when compared with the 12 μg group (25 [86%] participants, 95% CI 69·4-94·5) for adjuvanted and non-adjuvanted groups. Common local reactions were tenderness (151 [84%] participants; 356 events, 95% CI 78·3-89·4) and injection site pain (120 [67%]; 224 events, 59·9-73·5); most frequent systemic reactions were headache (80 [45%]; 112 events, 37·6-52·0), excessive fatigue (45 [25%]; 56 events, 19·4-32·0), and myalgia (45 [25%]; 57 events, 19·4-32·0). A similar safety and tolerability profile was observed between adjuvanted and non-adjuvanted formulations. The majority of solicited adverse events were mild or moderate. VLA15 was immunogenic for all OspA serotypes with higher immune responses induced in the adjuvanted higher dose groups (geometric mean titre range 90 μg with alum 61·3 U/mL-321·7 U/mL vs 23·8 U/mL-111·5 U/mL at 90 μg without alum).
INTERPRETATION
This novel multivalent vaccine candidate against Lyme borreliosis was safe and immunogenic and paves the way to further clinical development.
FUNDING
Valneva Austria.
Topics: Adult; Humans; Bacterial Vaccines; Lyme Disease; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Myalgia; Double-Blind Method; Immunogenicity, Vaccine; Antibodies, Viral
PubMed: 37419129
DOI: 10.1016/S1473-3099(23)00210-4 -
Methods in Molecular Biology (Clifton,... 2022The use of emulsion as adjuvants is widely used in veterinary vaccines. Emulsion adjuvants are inexpensive, stable, and relatively easy to prepare into vaccine...
The use of emulsion as adjuvants is widely used in veterinary vaccines. Emulsion adjuvants are inexpensive, stable, and relatively easy to prepare into vaccine formulations. Here we describe the preparation of oil-in-water emulsion adjuvant that has been shown to enhance immune responses and protect against diseases in pigs. This emulsion adjuvant and its variations could potentially be used alone or in combination with other adjuvants in veterinary vaccine formulations.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Animals; Emulsions; Swine; Vaccines
PubMed: 34918248
DOI: 10.1007/978-1-0716-1892-9_11