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Frontiers in Immunology 2023Vaccine adjuvant research is being fueled and driven by progress in the field of innate immunity that has significantly advanced in the past two decades with the... (Review)
Review
Vaccine adjuvant research is being fueled and driven by progress in the field of innate immunity that has significantly advanced in the past two decades with the discovery of countless innate immune receptors and innate immune pathways. Receptors for pathogen-associated molecules (PAMPs) or host-derived, danger-associated molecules (DAMPs), as well as molecules in the signaling pathways used by such receptors, are a rich source of potential targets for agonists that enable the tuning of innate immune responses in an unprecedented manner. Targeted modulation of immune responses is achieved not only through the choice of immunostimulator - or select combinations of adjuvants - but also through formulation and systematic modifications of the chemical structure of immunostimulatory molecules. The use of medium and high-throughput screening methods for finding immunostimulators has further accelerated the identification of promising novel adjuvants. However, despite the progress that has been made in finding new adjuvants through systematic screening campaigns, the process is far from perfect. A major bottleneck that significantly slows the process of turning confirmed or putative innate immune receptor agonists into vaccine adjuvants continues to be the lack of defined correlates of adjuvanticity. This brief review discusses recent developments, exciting trends, and notable successes in the adjuvant research field, albeit acknowledging challenges and areas for improvement.
Topics: Adjuvants, Immunologic; Immunity, Innate; Adjuvants, Pharmaceutic; Receptors, Immunologic; Signal Transduction
PubMed: 36742311
DOI: 10.3389/fimmu.2023.1105655 -
Current Opinion in Pharmacology Oct 2019The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs. A lack of innovation and investment... (Review)
Review
The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs. A lack of innovation and investment for almost 50 years has led to significant efforts currently being devoted to find alternative and innovative therapies to face this challenge. This short review highlights some of the recent efforts to develop synthetic small molecules with anti-infective activity. This article is focused on those compounds that, when co-administered with an antibiotic, enhance the antimicrobial action of the drug, as well as compounds that target unexplored objectives for bacterial survival. Selected examples are provided.
Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Bacterial Infections; Humans
PubMed: 31005786
DOI: 10.1016/j.coph.2019.03.004 -
Frontiers in Immunology 2019Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung.... (Review)
Review
Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5' ectonucleotidase (CD73) that catabolize ATP to adenosine. An acute CD73-dependent increase of adenosine in normal tissues mostly exerts tissue protective functions whereas chronically increased adenosine-levels in tissues exposed to DNA damaging chemotherapy or radiotherapy promote pathologic remodeling processes and fibrosis for example in the skin and the lung. Importantly, cancer cells also express CD73 and high CD73 expression in the tumor tissue has been linked to poor overall survival and recurrence free survival in patients suffering from breast and ovarian cancer. CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cancer cells. In addition, adenosine can promote tumor intrinsic or therapy-induced immune escape by various mechanisms that dampen the immune system. Consequently, modulating CD73 or cancer-derived adenosine in the tumor microenvironment emerges as an attractive novel therapeutic strategy to limit tumor progression, improve antitumor immune responses, avoid therapy-induced immune deviation, and potentially limit normal tissue toxicity. However, the role of CD73/adenosine signaling in the tumor and normal tissue responses to radiotherapy and its use as therapeutic target to improve the outcome of radiotherapy approaches is less understood. The present review will highlight the dual role of CD73 and adenosine in tumor and tissue responses to radiotherapy with a special focus to the lung. It will also discuss the potential benefits and risks of pharmacologic modulation of the CD73/adenosine system to increase the therapeutic gain of radiotherapy or combined radioimmunotherapy in cancer treatment.
Topics: 5'-Nucleotidase; Adenosine; Adjuvants, Pharmaceutic; Animals; Humans; Immunomodulation; Molecular Targeted Therapy; Radiotherapy; Receptors, Purinergic P1; Signal Transduction
PubMed: 31024543
DOI: 10.3389/fimmu.2019.00698 -
Cells Jan 2023Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to... (Review)
Review
Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to greatly improve patient outcomes in mismatch repair-deficient (dMMR) CRC. Now, they are part of the standard of care for this subset of CRC. Because of this, there has been a growing interest in the efficacy and timing of immunotherapy for other subsets of CRC, including locally advanced, metastatic, and microsatellite stable (MSS). In this review, we aim to examine the three main classes of immunotherapy for CRC-immune checkpoint inhibitors (ICIs), adoptive cell transfer therapy (ACT), and tumor vaccines-and discuss the most recent advances and future directions for each.
Topics: Humans; Neoadjuvant Therapy; Immune Checkpoint Inhibitors; Immunotherapy; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Colorectal Neoplasms
PubMed: 36672193
DOI: 10.3390/cells12020258 -
Frontiers in Immunology 2023The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with...
Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors.
BACKGROUND
The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs).
METHODS
HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted.
RESULTS
A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% ( < 0.001) and 54.2% vs. 25.1% ( = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% ( = 0.001) and 84.3% vs. 55.5% ( = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT.
CONCLUSIONS
PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Tyrosine Kinase Inhibitors; Retrospective Studies; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Treatment Outcome
PubMed: 37359534
DOI: 10.3389/fimmu.2023.1202039 -
International Journal of Molecular... Apr 2021Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many... (Review)
Review
Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.
Topics: Adjuvants, Pharmaceutic; Anti-Infective Agents, Local; Bandages; Biocompatible Materials; Humans; Hydrogels; Nanomedicine; Nanoparticles; Neovascularization, Physiologic; Phytotherapy; Re-Epithelialization; Regeneration; Skin; Skin Physiological Phenomena; Skin Transplantation; Wound Closure Techniques; Wound Healing; Wound Infection
PubMed: 33947121
DOI: 10.3390/ijms22094748 -
Medicine Aug 2023The issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was to assess the efficiency and safety of acupuncture and moxibustion in PMD patients.
METHODS
Databases, namely PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, CBM, VIP, and WanFang, were reviewed for related randomized controlled trials dated between database inception and November 22, 2022. The primary outcomes were the efficacy rate and the Hamilton Depression Scale score. The secondary outcomes were the levels of follicle-stimulating hormone, luteinizing hormone, and estradiol and the Kupperman score. Odds ratios (ORs) were generated as the effect size for dichotomous outcomes, while the standard mean difference (SMD) ± standard deviation was used for continuous outcomes. Matrices were developed to demonstrate pairwise comparisons of regimens related to each endpoint. Utilizing Review Manager (RevMan) 5.3, Stata 16.0 and SPSS 21, data were analyzed.
RESULTS
In total, 27 studies involving 2269 PMD patients and 8 therapeutic measures were incorporated into the network meta-analysis (NMA). The NMA showed that warm acupuncture (OR = 1.55, 95% CI: 1.00-2.44), electroacupuncture (OR = 1.34, 95% CI: 1.00-1.8), abdominal acupuncture (OR = 1.19, 95% CI: 0.73-1.96), and common acupuncture (OR = 1.4, 95% CI: 0.9-2.17) were more effective than fluoxetine + menopausal hormone treatment in the treatment of PMD. The NMA also showed that, based on the Hamilton Depression Scale score, warm acupuncture was more effective than the other 4 acupuncture-related treatments, i.e., electroacupuncture (SMD = -1.22, 95% CI: -2.34 to -0.09), thread embedding (SMD = -1.31, 95% CI: -2.21 to -0.40), abdominal acupuncture (SMD = -1.33, 95% CI: -2.42 to -0.24), and common acupuncture (SMD = -1.46, 95% CI: -2.26 to -0.66). The cumulative ranking probability (SUCRA) showed that warm acupuncture (99.6%) was the best treatment method.
CONCLUSIONS
The findings of this network meta-analysis may help patients and therapists choose the best acupuncture therapy for treating perimenopausal depression patients and furnish reliable evidence for guidelines.
Topics: Humans; Network Meta-Analysis; Depression; Perimenopause; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Acupuncture Therapy
PubMed: 37603500
DOI: 10.1097/MD.0000000000034694 -
Frontiers in Immunology 2023Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular...
Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces nasal colonization.
INTRODUCTION
Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular pertussis vaccines (aPV) delivered intramuscularly reduce bacterial numbers in the lungs of immunized animals and humans, but do not reduce nasal colonization. Thus, aPV-immunized individuals are sources of community transmission. We showed previously that modification of a commercial aPV (Boostrix) by addition of the Th1/17 polarizing adjuvant Bordetella Colonization Factor A (BcfA) attenuated Th2 responses elicited by alum and accelerated clearance of B. pertussis from mouse lungs. Here we tested whether a heterologous immunization strategy with systemic priming and mucosal booster (prime-pull) would reduce nasal colonization.
METHODS
Adult male and female mice were immunized intramuscularly (i.m.) with aPV or aPV/BcfA and boosted either i.m. or intranasally (i.n.) with the same formulation. Tissue-resident memory (TRM) responses in the respiratory tract were quantified by flow cytometry, and mucosal and systemic antibodies were quantified by ELISA. Immunized and naïve mice were challenged i.n. with Bordetella pertussis and bacterial load in the nose and lungs enumerated at days 1-14 post-challenge.
RESULTS
We show that prime-pull immunization with Boostrix plus BcfA (aPV/BcfA) generated IFNγ+ and IL-17+ CD4+ lung resident memory T cells (TRM), and CD4+IL-17+ TRM in the nose. In contrast, aPV alone delivered by the same route generated IL-5+ CD4+ resident memory T cells in the lungs and nose. Importantly, nasal colonization was only reduced in mice immunized with aPV/BcfA by the prime-pull regimen.
CONCLUSIONS
These results suggest that TH17 polarized TRM generated by aPV/BcfA may reduce nasal colonization thereby preventing pertussis transmission and subsequent resurgence.
Topics: Animals; Female; Male; Mice; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Bordetella pertussis; CD4-Positive T-Lymphocytes; Interleukin-17; Pertussis Vaccine; Whooping Cough
PubMed: 37275891
DOI: 10.3389/fimmu.2023.1181876 -
Frontiers in Immunology 2023Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine...
BACKGROUND
Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.
METHODS AND RESULTS
To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.
CONCLUSIONS
This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.
Topics: Humans; Animals; Mice; Immunity, Humoral; T Follicular Helper Cells; alpha-Tocopherol; Squalene; Emulsions; SARS-CoV-2; COVID-19; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 36891311
DOI: 10.3389/fimmu.2023.1116238 -
Immunotherapy Nov 2009Toll-like receptors (TLRs) are pattern-recognition receptors related to the Drosophila Toll protein. TLR activation alerts the immune system to microbial products and... (Review)
Review
Toll-like receptors (TLRs) are pattern-recognition receptors related to the Drosophila Toll protein. TLR activation alerts the immune system to microbial products and initiates innate and adaptive immune responses. The naturally powerful immunostimulatory property of TLR agonists can be exploited for active immunotherapy against cancer. Antitumor activity has been demonstrated in several cancers, and TLR agonists are now undergoing extensive clinical investigation. This review discusses recent advances in the field and highlights potential opportunities for the clinical development of TLR agonists as single agent immunomodulators, vaccine adjuvants and in combination with conventional cancer therapies.
Topics: Adjuvants, Pharmaceutic; Animals; Antineoplastic Agents; Drug Therapy, Combination; Humans; Immunomodulation; Neoplasms; Toll-Like Receptors
PubMed: 20563267
DOI: 10.2217/imt.09.70