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Signal Transduction and Targeted Therapy Jul 2023Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms are not yet clear. With a greater understanding of the... (Review)
Review
Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms are not yet clear. With a greater understanding of the mechanisms by which the innate immune response controls the antigen-specific response, the adjuvants' action mechanisms are beginning to be elucidated. Adjuvants can be categorized as immunostimulants and delivery systems. Immunostimulants are danger signal molecules that lead to the maturation and activation of antigen-presenting cells (APCs) by targeting Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) to promote the production of antigen signals and co-stimulatory signals, which in turn enhance the adaptive immune responses. On the other hand, delivery systems are carrier materials that facilitate antigen presentation by prolonging the bioavailability of the loaded antigens, as well as targeting antigens to lymph nodes or APCs. The adjuvants' action mechanisms are systematically summarized at the beginning of this review. This is followed by an introduction of the mechanisms, properties, and progress of classical vaccine adjuvants. Furthermore, since some of the adjuvants under investigation exhibit greater immune activation potency than classical adjuvants, which could compensate for the deficiencies of classical adjuvants, a summary of the adjuvant platforms under investigation is subsequently presented. Notably, we highlight the different action mechanisms and immunological properties of these adjuvant platforms, which will provide a wide range of options for the rational design of different vaccines. On this basis, this review points out the development prospects of vaccine adjuvants and the problems that should be paid attention to in the future.
Topics: Adjuvants, Vaccine; Vaccines; Adjuvants, Immunologic; Immunity, Innate; Toll-Like Receptors
PubMed: 37468460
DOI: 10.1038/s41392-023-01557-7 -
Expert Review of Vaccines Apr 2011Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells... (Review)
Review
Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimized by maintaining ODNs and vaccine in close proximity. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally, and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. Clinical trials demonstrate that CpG ODNs have a good safety profile and increase the immunogenicity of coadministered vaccines.
Topics: Adjuvants, Immunologic; Clinical Trials as Topic; Communicable Disease Control; Humans; Neoplasms; Oligodeoxyribonucleotides; Vaccines
PubMed: 21506647
DOI: 10.1586/erv.10.174 -
Cells Jan 2022Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use.... (Review)
Review
Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.
Topics: Adjuvants, Immunologic; Desensitization, Immunologic; Humans; Immunization; Peptides; Proteomics; Treatment Outcome
PubMed: 35053328
DOI: 10.3390/cells11020212 -
Pharmacological Research Oct 2015Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time.... (Review)
Review
Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.
Topics: Adjuvants, Immunologic; Animals; Autoimmune Diseases; Autoimmunity; Humans; Vaccination; Vaccines
PubMed: 26275795
DOI: 10.1016/j.phrs.2015.08.003 -
Frontiers in Immunology 2023In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of... (Review)
Review
In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.
Topics: Humans; Adjuvants, Vaccine; Vaccines; Immunization; Vaccination; Adjuvants, Immunologic
PubMed: 36911719
DOI: 10.3389/fimmu.2023.1043109 -
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 -
Human Vaccines & Immunotherapeutics 2015In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum... (Review)
Review
In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Aluminum Hydroxide; Biomedical Research; Humans; Immunity, Innate; Vaccines
PubMed: 25692535
DOI: 10.1080/21645515.2014.1004026 -
The New England Journal of Medicine Jun 2022Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine.
METHODS
In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.
RESULTS
A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).
CONCLUSIONS
The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).
Topics: Adjuvants, Immunologic; Adjuvants, Vaccine; Adult; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Double-Blind Method; Humans; Injections, Intramuscular; SARS-CoV-2; Vaccination
PubMed: 35507508
DOI: 10.1056/NEJMoa2201300 -
Drug Discovery Today. Technologies Dec 2020Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being... (Review)
Review
Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being especially suitable for the development of vaccines against intracellular pathogens where alum is useless. The development of new adjuvants is difficult and expensive, however, in the last two years, seven new carbohydrate-based adjuvants have been patented, also there are twelve ongoing clinical trials of vaccines that contain carbohydrate-based adjuvants, as well as numerous publications on their mechanism of action and safety. More research is necessary to improve the existent adjuvants and develop innovative ones.
Topics: Adjuvants, Immunologic; Animals; Carbohydrates; Clinical Trials as Topic; Drug Development; Drug Evaluation, Preclinical; Humans; Immunity, Cellular; Immunity, Humoral; Models, Animal; Vaccination
PubMed: 33388128
DOI: 10.1016/j.ddtec.2020.09.005 -
Current Opinion in Allergy and Clinical... Dec 2022The purpose of this article is to provide an overview of the literature pertaining to the use of MicroCrystalline Tyrosine (MCT) in the immunotherapy with an emphasis on... (Review)
Review
PURPOSE OF REVIEW
The purpose of this article is to provide an overview of the literature pertaining to the use of MicroCrystalline Tyrosine (MCT) in the immunotherapy with an emphasis on recent developments.
RECENT FINDINGS
In addition to significant effectiveness and safety profiles, additional aspects of interest such as booster immunotherapy concepts, sustained clinical effects, long-term efficacy and disease-modifying effects are being focused on in the recently published studies. The depot adjuvant MCT also shows potential in promising disease-challenge models such as for malaria and melanoma.
SUMMARY
MCT-adsorbed immunotherapy products have been shown to provide convincing overall safety, tolerability and efficacy outcomes, as well in vulnerable groups such as children and asthmatic patients.
Topics: Child; Humans; Tyrosine; Immunotherapy; Adjuvants, Immunologic; Immunologic Factors; Asthma
PubMed: 36254926
DOI: 10.1097/ACI.0000000000000859