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Biomolecules Aug 2020There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis,... (Review)
Review
There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.
Topics: Adjuvants, Pharmaceutic; Animals; Anti-Inflammatory Agents; Antioxidants; COVID-19; Coronavirus Infections; Homeostasis; Humans; Melatonin; Pandemics; Pneumonia, Viral
PubMed: 32825327
DOI: 10.3390/biom10091211 -
Theranostics 2021Antimicrobial resistance has been a global health challenge that threatens our ability to control and treat life-threatening bacterial infections. Despite ongoing... (Review)
Review
Antimicrobial resistance has been a global health challenge that threatens our ability to control and treat life-threatening bacterial infections. Despite ongoing efforts to identify new drugs or alternatives to antibiotics, no new classes of antibiotic or their alternatives have been clinically approved in the last three decades. A combination of antibiotics and non-antibiotic compounds that could inhibit bacterial resistance determinants or enhance antibiotic activity offers a sustainable and effective strategy to confront multidrug-resistant bacteria. In this review, we provide a brief overview of the co-evolution of antibiotic discovery and the development of bacterial resistance. We summarize drug-drug interactions and uncover the art of repurposing non-antibiotic drugs as potential antibiotic adjuvants, including discussing classification and mechanisms of action, as well as reporting novel screening platforms. A pathogen-by-pathogen approach is then proposed to highlight the critical value of drug repurposing and its therapeutic potential. Finally, general advantages, challenges and development trends of drug combination strategy are discussed.
Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Bacterial Infections; Drug Interactions; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans
PubMed: 33754035
DOI: 10.7150/thno.56205 -
Cells Aug 2023In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and... (Review)
Review
In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development.
Topics: Humans; Cancer Vaccines; Immunotherapy; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antibodies, Monoclonal; Neoplasms
PubMed: 37681891
DOI: 10.3390/cells12172159 -
Methods in Molecular Biology (Clifton,... 2023Self-adjuvanting vaccines, covalent conjugates between antigens and adjuvants, are chemically well-defined compared with conventional vaccines formulated through mixing... (Review)
Review
Self-adjuvanting vaccines, covalent conjugates between antigens and adjuvants, are chemically well-defined compared with conventional vaccines formulated through mixing antigens with adjuvants. Innate immune receptor ligands effectively induce acquired immunity through the activation of innate immunity, thereby enhancing host immune responses. Thus, innate immune receptor ligands are often used as adjuvants in self-adjuvanting vaccines. In a self-adjuvanting vaccine, the covalent linkage of antigen and adjuvant enables their simultaneous uptake into immune cells where the adjuvant consequently induces antigen-specific immune responses. Importantly, self-adjuvanting vaccines do not require immobilization to carrier proteins or co-administration of additional adjuvants and thus avoid inducing undesired immune responses. Because of these excellent properties, self-adjuvanting vaccines are expected to be candidates for next-generation vaccines. Here, we take an overview of vaccine adjuvants, mainly focusing on those utilized in self-adjuvanting vaccines and then we review recent reports on self-adjuvanting conjugate vaccines.
Topics: Vaccines, Conjugate; Vaccines; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Immunity, Innate; Ligands
PubMed: 36587070
DOI: 10.1007/978-1-0716-2910-9_5 -
MMW Fortschritte Der Medizin Oct 2022
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Humans; Influenza, Human; Sports; Vaccination
PubMed: 36198944
DOI: 10.1007/s15006-022-1937-1 -
MMW Fortschritte Der Medizin Nov 2023
Topics: Humans; Ascorbic Acid; Vitamins; Combined Modality Therapy; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Neoplasms
PubMed: 37973748
DOI: 10.1007/s15006-023-3142-2 -
The Journal of Infectious Diseases Dec 2022Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years.
METHODS
Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.
RESULTS
All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.
CONCLUSIONS
RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.
Topics: Humans; Aged; Respiratory Syncytial Virus Vaccines; Viral Fusion Proteins; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Antibodies, Viral; Respiratory Syncytial Virus, Human; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 35543281
DOI: 10.1093/infdis/jiac189 -
International Journal of Pharmaceutics Feb 2023The majority of vaccines have been delivered into the muscular tissue. Skin contains large amounts of antigen-presenting cells and has been recognized as a more... (Review)
Review
The majority of vaccines have been delivered into the muscular tissue. Skin contains large amounts of antigen-presenting cells and has been recognized as a more immunogenic site for vaccine delivery. Intradermal delivery has been approved to improve influenza vaccine efficacy and spare influenza vaccine doses. In response to the recent monkeypox outbreak, intradermal delivery has been also approved to stretch the limited monkeypox vaccine doses to immunize more people at risk. Incorporation of vaccine adjuvants is promising to further increase intradermal vaccine efficacy and spare more vaccine doses. Yet, intradermal vaccination is associated with more significant local reactions than intramuscular vaccination. Thus, adjuvants suitable to boost intradermal vaccination need to have a good local safety without inducing overt local reactions. This review introduces currently approved adjuvants in licensed human vaccines and their relative reactogenicity for intradermal delivery and then introduces emerging chemical and physical adjuvants with a good local safety to boost intradermal vaccination. The rational to develop physical adjuvants, the types of physical adjuvants, and the unique advantages of physical adjuvants to boost intradermal vaccination are also introduced in this review.
Topics: Humans; Influenza Vaccines; Vaccination; Skin; Influenza, Human; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Injections, Intradermal
PubMed: 36586639
DOI: 10.1016/j.ijpharm.2022.122559 -
Journal of Biomedical Nanotechnology Sep 2014Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical... (Review)
Review
Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes.
Topics: Adjuvants, Pharmaceutic; Animals; Biocompatible Materials; Humans; Inorganic Chemicals; Nanostructures; Organic Chemicals; Pharmaceutical Preparations
PubMed: 25429253
DOI: 10.1166/jbn.2014.1898 -
Frontiers in Immunology 2023Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative... (Review)
Review
Allergen-specific immunotherapy (AIT) describes the establishment of peripheral tolerance through repeated allergen exposure, which qualifies as the only curative treatment for allergic diseases. Although conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been approved to treat respiratory allergies clinically, the progress made is far from satisfactory. Epicutaneous immunotherapy (EPIT) exploits the skin's immune properties to modulate immunological response, which is emerging as a promising alternative and has shown effectiveness in many preclinical and clinical studies for both respiratory and food allergies. It is worth noting that the stratum corneum (SC) barrier impedes the effective delivery of allergens, while disrupting the SC layer excessively often triggers unexpected Th2 immune responses. This work aims to comprehend the immunological mechanisms of EPIT, and summarize the innovative system for sufficient delivery of allergens as well as tolerogenic adjuvants. Finally, the safety, acceptability, and cost-effectiveness of these innovative delivery systems are discussed, which directs the development of future immunotherapies with all desirable characteristics.
Topics: Humans; Hypersensitivity; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Desensitization, Immunologic; Epidermis
PubMed: 37675117
DOI: 10.3389/fimmu.2023.1238022