Safe Adjuvant Research Articles

Comparative Study to Evaluate the Efficacy of Dexmedetomidine and Magnesium Sulfate as Adjuvants to 0.5% of Hyperbaric Bupivacaine in Patient Undergoing Abdominal Hysterectomy by Spinal Anesthesia: A Randomized, Double-blind Study

Abstract Objective: Abdominal hysterectomy is a common gynecological procedure. While spinal anesthesia offers pain relief, its short analgesic effect is limiting. In this context, there are not many research that examined magnesium sulfate, dexmedetomidine, and 0.5% hyperbaric bupivacaine. Our research addresses this gap as “Comparing Dexmedetomidine and Magnesium Sulfate as Adjuvants to Hyperbaric Bupivacaine for Abdominal Hysterectomy”. Methods: Ninety patients with the American Society of Anesthesiologists Classification I and II, aged 30–60, planned for abdominal hysterectomy were randomized to either dexmedetomidine or magnesium sulfate or control group as adjuvants to hyperbaric bupivacaine. The primary objective was to find the effectiveness of the anesthesia in terms of both sensory and motor blocks (onset, duration, and severity), with the secondary objective was to find out any other associated complications. Results: In comparison to the magnesium sulfate group, the dexmedetomidine group’s anesthetic effect began significantly more immediately and persisted much longer (P < 0.001). The groups did not vary statistically significant in terms of side effects or hemodynamic instability. Conclusion: Adjuvants such as dexmedetomidine or magnesium sulfate along with hyperbaric bupivacaine, for abdominal hysterectomy under spinal anesthesia, provide effective anesthesia. Dexmedetomidine (10 μg) and magnesium sulfate (100 mg) both showed safe intrathecal adjuvant usage. Remarkably, dexmedetomidine surpasses magnesium sulfate by swiftly inducing sensory and motor blocks, extending their duration, and enhancing analgesia. Notably, both adjuncts yield no adverse effects. Overall, these findings underscore the potential of dexmedetomidine as a more effective adjuvant in spinal anesthesia protocols for abdominal hysterectomy procedures.

Spleen-Targeted mRNA Vaccine Doped with Manganese Adjuvant for Robust Anticancer Immunity In Vivo.

The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this "All-in-One" mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.

Effectiveness of a new commercial ocular spray containing Biosecur in reducing conjunctival microbial flora as surgical prophylaxis in patients undergoing cataract surgery

IntroductionThis study is aimed to evaluate the antiseptic activity of a new ophthalmic spray containing Biosecur citrus extract as a preoperative prophylactic treatment in patients undergoing cataract intervention.MethodsA prospective, multicenter study was conducted. Patients applied Oftasecur spray on the eye scheduled for surgery, three times daily for 3 days before surgery. Conjunctival swabs were performed before and after the treatment. Qualitative and quantitative microbiological analyses were assessed.ResultsHundred and forty-seven patients (M: F = 76:71; mean age 70.74 ± 9.41 years) were enrolled. 58.5% of patients presented detectable microbial loads in the eye to be operated, before treatment. Most predominant bacterial species were: Staphylococcus epidermidis, coagulase-negative Staphylococci and Staphylococcus aureus. Patients were divided into three subgroups, according to the microbial loads measured at baseline: lower than 10 CFU/ml (41.7%), between 10 and 100 CFU/ml (31.7%), equal or greater than 100 CFU/ml (26.6%). A twofold reduction in positive patients who received Oftasecur: 44 eyes (51.2%) resulted in negative after ocular treatment. A significant reduction in bacterial loads was observed (p < 0.001). No ocular adverse reactions were recorded.ConclusionOftasecur spray effectively reduced conjunctival bacterial burden. It may represent a proper and safe antiseptic adjuvant treatment in patients undergoing cataract surgery.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral delivery system for H9N2 vaccine to promote systemic and mucosal immune response.

Most infectious diseases are caused by pathogens that invade the body tissues through mucosal tract. Therefore, it is essential to develop effective vaccines administered through the mucosa as a first-line of defense against major infectious diseases. Oral delivery of vaccines is currently of great interest due to its potential to elicit both mucosal and systemic immune responses, high compliance rate and non-invasive nature. However, their development is limited by the challenging gastrointestinal (GI) environment, the low permeability of the mucus barrier, and the lack of effective and safe mucosal adjuvants. Currently, nanoparticle-based strategies show significant potential for improving oral vaccine delivery systems. Herein, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were developed for oral delivery of H9N2 antigen. CDP-DFNS induced the activation of macrophages, thereby enhancing antigen uptake in vitro. Additionally, CDP-DFNS/H9N2 significantly activated the dendritic cells (DCs) in Peyer's patches (PPs), and T/B cells in mesenteric lymph nodes (MLNs). Moreover, CDP-DFNS/H9N2 enhanced the HI titers and levels of H9N2-specific antibody IgG, secretory IgA (SIgA) and H9N2-specific IgA in intestinal and respiratory mucosa, as well as Th-associated cytokines. Our results indicate that CDP-DFNS could be a promising oral vaccine adjuvant delivery system.

Intranasal immunization with CPAF combined with cyclic-di-AMP induces a memory CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum.

Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants. To address this need, we produced CPAF in a cell-free protein synthesis platform and adjuvanted it with the TLR9-agonist CpG1826, STING (stimulator of interferon genes) agonist cyclic-di-AMP (CDA), and/or the squalene oil-in-water nanoemulsion, AddaS03. We determined that intranasal immunization with CPAF plus CDA was well tolerated in female mice, induced CD4 T cells that produced IL-17A or IFNγ, significantly reduced bacterial shedding, and shortened the duration of infection in mice intravaginally challenged with Chlamydia muridarum . These data demonstrate the potential for CDA as a mucosal adjuvant for vaccines against Chlamydia genital tract infection.

Proanthocyanidins-based adjuvant for enhanced immune responses of SARS-CoV-2 subunit vaccine

Aluminum-containing adjuvants have been widely used in human vaccines, such as anti-COVID-19 vaccine, to enhance antigen-specific immune responses. However, a major limitation of aluminum adjuvants in clinical application is that they typically enhance humoral immune responses but have weaker effects on cellular immune responses. Therefore, there has been a continuous and active pursuit of novel adjuvants that can address the shortcomings of traditional adjuvants and improve vaccine efficacy. In this paper, we proposed a novel vaccine-adjuvant system utilizing the convenient physical mixing of natural proanthocyanidins (PCs) and its derivative with a recombinant RBD subunit vaccine, which induced comparable humoral immune responses compared to aluminum adjuvant. In the context of cellular immunity, PCs modified with 4-bromomethyl phenylboronic acid not only enhanced the maturation and migration of dendritic cells but also improved the antigen uptake and presentation capacity of monocytes, leading to robust activation of immune cells, particularly involving CD4+ and CD8+ T cells, thereby demonstrating a clear Th1/CTL response bias. In general, PCs andtheir derivatives could be potential innovative natural adjuvants which effectively balance the Th1/Th2 immune response to recompense for the deficiency of aluminum adjuvant, and our study also offers an approach to discovering safe and efficient natural adjuvants.

Oral magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus

BackgroundSystemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping.ResultsMRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology.ConclusionIn conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLE.

Intranasal Delivery of Quillaja brasiliensis Saponin-Based Nanoadjuvants Improve Humoral Immune Response of Influenza Vaccine in Aged Mice.

Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines.

Pickering emulsion-guided monomeric delivery of monophosphoryl lipid A for enhanced vaccination

Immunological adjuvants are vaccine components that enhance long-lasting adaptive immune responses to weakly immunogenic antigens. Monophosphoryl lipid A (MPLA) is a potent and safe vaccine adjuvant that initiates an early innate immune response by binding to the Toll-like receptor 4 (TLR4). Importantly, the binding and recognition process is highly dependent on the monomeric state of MPLA. However, current vaccine delivery systems often prioritize improving the loading efficiency of MPLA, while neglecting the need to maintain its monomeric form for optimal immune activation. Here, we introduce a Pickering emulsion-guided MPLA monomeric delivery system (PMMS), which embed MPLA into the oil-water interface to achieve the monomeric loading of MPLA. During interactions with antigen-presenting cells, PMMS functions as a chaperone for MPLA, facilitating efficient recognition by TLR4 regardless of the presence of lipopolysaccharide-binding proteins. At the injection site, PMMS efficiently elicited local immune responses, subsequently promoting the migration of antigen-internalized dendritic cells to the lymph nodes. Within the draining lymph nodes, PMMS enhanced antigen presentation and maturation of dendritic cells. In C57BL/6 mice models, PMMS vaccination provoked potent antigen-specific CD8+ T cell-based immune responses. Additionally, PMMS demonstrated strong anti-tumor effects against E.G7-OVA lymphoma. These data indicate that PMMS provides a straightforward and efficient strategy for delivering monomeric MPLA to achieve robust cellular immune responses and effective cancer immunotherapy.

Advances in vaccine development for Chlamydia trachomatis.

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection globally. Antibiotic treatment is highly effective, but infection is often asymptomatic resulting in most individuals going undetected and untreated. This untreated infection can ascend to the upper female genital tract to cause pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. Chlamydia screening and treatment programs have failed to control this epidemic and demonstrate the need for an efficacious vaccine to prevent transmission and disease. Animal models and human epidemiological data reveal that natural immunity can provide partial or short-lived sterilizing immunity. These data further demonstrate the importance of eliciting interferon gamma (IFNγ)-producing cluster of differentiation 4 (CD4) T cells (Th1 and Th1/17 cells) that can likely synergize with antibody-mediated opsonophagocytosis to provide optimal protection. These studies have guided preclinical rational vaccine design for decades and the first Phase 1 clinical trials have recently been completed. Recent advances have led to improvements in vaccine platforms and clinically safe adjuvants that help provide a path forward. This review describes vaccine models, correlates of immunity, antigen and adjuvant selection, and future clinical testing for Chlamydia vaccine development.

Development of α-Tocopherol Loaded PLGA Nanoparticles and Its Evaluation as a Novel Immune Adjuvant.

With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α-Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8nm, polydispersity indexvalue of 0.042, and Zeta potential of -13.26mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.

Poly(allylamine)-tripolyphosphate polymeric nanoparticle as an NLRP3-dependent systemic adjuvant for the vaccine development.

Nanotechnology plays a crucial role in vaccine development and provides the opportunity to design functional nanoparticles (Np) of different compositions, sizes, charges and surface properties for biomedical applications. The present study aims to evaluate a complex coacervate-like Np composed of poly(allylamine hydrochloride) (PAH) and tripolyphosphate (Tpp) as a safe vehicle and adjuvant for systemic vaccines. We investigated the activation of different antigen-presenting cells (APCs) with Np-PAH and its adjuvanticity in Balbc/c and different KO mice that were intraperitoneally immunized with Np-OVA. We found that Np-PAH increased the expression of CD86 and MHCII and promoted the production and secretion of interleukin-1β (IL-1β) and IL-18 through the inflammasome NLRP3 when macrophages and dendritic cells were co-incubated with LPS and Np-PAH. We evidenced an unconventional IL-1β release through the autophagosome pathway. The inhibition of autophagy with 3-methyladenine reduced the LPS/Np-PAH-induced IL-1β secretion. Additionally, our findings showed that the systemic administration of mice with Np-OVA triggered a significant induction of serum OVA-specific IgG and IgG2a, an increased secretion of IFN-γ by spleen cells, and high frequencies of LT CD4 + IFN-γ + and LT CD8 + IFN-γ + . In conclusion, our findings show that PAH-based Np promoted the inflammasome activation of innate cells with Th1-dependent adjuvant properties, making them valuable for formulating of novel preventive or therapeutic vaccines for infectious and non-infectious diseases.

Role of Adjuvant Mitomycin C in The Endoscopic Treatment of Laryngotracheal Stenosis (Meta-Analytic Study)

Abstract Background Laryngotracheal stenosis is a life-threatening restriction in pulmonary ventilation. It is an umbrella term, including luminal compromise at the level of the larynx, subglottis, or trachea. Etiology of laryngotracheal stenosis is multifactorial. In adults and adolescents it is mostly acquired, where in children it may be acquired or congenital. Acquired laryngotracheal stenosis can result from previous intubation or tracheostomy, systemic disease, trauma, infection, or idiopathic causes. Historically, infectious etiology was common. Currently, laryngotracheal stenosis most frequently results from prolonged intubation or trauma from intubation itself. Objective To evaluate the effectiveness of topical Mitomycin C as an adjuvant treatment with the endoscopic management of laryngotreacheal stenosis. Patients and Methods The total number of patients in all the included studies was 454, 379 patients in MMC group and 75 patients in non-MMC group. Results This meta-analysis study showed that resolution (success) rate in MMC group was (68.7%) and there was a significant increase in resolution (success) rate in MMC compared to non- MMC group (p = 0.011) with the odds of being 5 times higher in MMC group (OR = 5.04). The Complications rate in MMC using patients was (4%). The result of this meta-analysis study showed that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results. Conclusion We suggest that that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results.

GFPBW1, a β-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous β-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 μg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 μg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

DNA programmed Mg-Al layered double hydroxide-based bi-adjuvant nanovaccines

Implementation of adjuvants is a requirement for inducing antigen-specific immune responses against infectious diseases. The conventional aluminum adjuvants used in clinical trials suffer from insufficient cellular immune response. Herein, we develop a bi-adjuvant nanovaccine containing receptor-binding domain (RBD) as antigen and DNA programmed Mg/Al layered double hydroxide (Mg/Al-LDH) as adjuvants, and thus achieve co-activation of potent humoral and cellular immune responses. The Mg/Al-LDH consisting of positively charged layers is firstly employed as scaffold to adsorb antigen via electrostatic interaction, and then CpG and dendritic cell (DC)-targeting aptamers co-encoded ultra-long DNA chains are easily decorated on the Mg/Al-LDH via interfacial assembly. The nanoscale formulations and interfacial targeting aptamers of nanovaccine facilitate their endocytosis by DC cells; the Mg/Al-LDH structure is acid-responsive and ensures the Al ions-inducing antigen cross-presentation for durable generation of antibody (Th2 immune response); and the agonist CpG in DNA chains can bind to the Toll-like receptor 9 (TLR 9) to activate cellular immunity (Th1 immune response). The bi-adjuvant nanovaccine fully combines the advantages of nanosheet alum-like adjuvant and precisely customization of DNA, and thus balances the Th1/Th2 immune response for compensating the deficiency of traditional alum adjuvant, providing a design guidance for creating next-generation of safe and efficient adjuvants in immunology.

N-acetylcysteine as a potentially safe adjuvant in the treatment of neurotoxicity due to pirimiphos-methyl poisoning.

Exogenous, well-established antioxidant N-acetylcysteine can reduce or prevent the deleterious effects of pesticides. In this study, utilizing a mouse model of daily single dose of N-acetylcysteine administration, we investigated the impact of this adjuvant on the treatment with atropine and/or obidoxime as well as oxidative stress response in pyrimiphos-methyl-induced toxicity. We found that N-acetylcysteine significantly reduces the oxidative stress generated by pyrimiphos-methyl. The therapy consisting of atropine and/or obidoxime routinely used in organophosphorous insecticide poisonings, including pyrimiphos-methyl, had no effect on the antioxidant properties of N-acetylcysteine. Adjunctive treatment offered by N-acetylcysteine fills therapeutic gap and may provide the full potential against pyrimiphos-methyl-induced toxicity.

Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae. Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.

Bevacizumab as Adjuvant Therapy in the Treatment of Keloid: A Randomized Clinical Trial

Background. Despite the availability of numerous therapies, keloid treatment remains a challenging clinical issue. Intralesional triamcinolone has been established as an effective corticosteroid treatment for keloids, while sporadic reports suggest the efficacy of intralesional verapamil. This study aimed to evaluate the safety and efficacy of bevacizumab as an adjuvant therapy for keloid treatment. Methods. This randomized controlled trial involved 38 patients diagnosed with keloid according to clinical criteria. The study compared the effects of intralesional triamcinolone combined with bevacizumab injections with intralesional triamcinolone alone. Patients were randomly assigned to either the combination treatment group, which received intralesional triamHEXAL® (20 mg/ml, every two weeks for three months) plus Avastin® (2.5 mg/ml, every two weeks for two months), or the single treatment group, which received intralesional triamHEXAL® alone. The Vancouver Scar Scale (VSS) was used for serial photographic records of scar evaluation, with differences in VSS scores considered the primary outcome, and changes in height and patient satisfaction visual analog score (VAS) were secondary outcomes. Results. A total of 38 patients participated, with a mean age (SD) of 35.32 (14.02) years and 50% male. No significant differences in age, BMI, disease duration, gender, causing, family history, or site were observed between the two groups. The single treatment group exhibited a mean reduction of 0.60 (95% CI: (−1.18, −0.01); P=0.045) in pigmentation score and a mean decrease of 1.37 (95% CI: (−2.68, −0.07); P=0.039) in total score compared to the combination treatment group after three months of treatment. There was a significant reduction in keloid height in the combination group after the end of the treatment (P=0.024). No significant differences in side effects were observed between the two groups. Conclusion. Our study demonstrates that bevacizumab can be considered an effective and safe adjuvant therapy option for keloid treatment, suggesting its potential as a promising treatment for the management of keloids. This trial is registered with IRCT20131119015455N5.

Boosting humoral and cellular immunity with enhanced STING activation by hierarchical mesoporous metal-organic framework adjuvants

Vaccination is essential for preventing and controlling infectious diseases, along with reducing mortality. Developing safe and versatile adjuvants to enhance humoral and cellular immune responses to vaccines remains a key challenge in vaccine development. Here, we designed hierarchical mesoporous MOF-801 (HM801) using a Cocamidopropyl betaine (CAPB) and a Pluronics F127 in an aqueous phase system. Meanwhile, we synthesized a novel SARS-CoV-2 nanovaccine (R@M@HM801) with a high loading capacity for both the STING agonist (MSA-2) and the Delta receptor binding domain (Delta-RBD) antigen. R@M@HM801 enhanced MSA-2 and RBD utilization and effectively co-delivered MSA-2 and RBD antigens to antigen-presenting cells in the draining lymph nodes, thereby promoting the activation of both T and B cells. Lymphocyte single-cell analysis showed that R@M@HM801 stimulated robust CD11b+CD4+ T cells, CXCR5+CD4+ T follicular helper (Tfh), and durable CD4+CD44+CD62L−, CD8+CD44+CD62L− effector memory T cell (TEM) immune responses, and promoted the proliferative activation of CD26+ B cells in vivo. Meanwhile, R@M@HM801 induced stronger specific antibodies and neutralization of pseudovirus against Delta compared to the RBD + MAS-2 and RBD + MAS-2 + Alum vaccines. Our study demonstrated the efficacy of a hierarchical mesoporous HM801 and its potential immune activation mechanism in enhancing adaptive immune responses against viruses and other diseases.

Process Optimization of Scaled-Up Production and Biosafety Evaluation of the Dimethyl-Dioctadecyl-Ammonium Bromide/Poly(lactic acid) Nano-Vaccine.

Nano-adjuvant vaccines could induce immune responses and enhance immunogenicity. However, the application and manufacturing of nano-adjuvant is hampered by its challenging scale-up, poor reproducibility, and low security. Therefore, the present study aimed to optimize the preparation nanoparticles (NPs) using FDA-approved biopolymer materials poly(lactic acid) (PLA) and cationic lipid didodecyl-dimethyl-ammonium bromide (DDAB), develop the scale-up process, and evaluate the stability and biosafety of it. The optimum preparation conditions of DDAB/PLA NPs on a small scale were as follows: DDAB amount of 30 mg, aqueous phase volume of 90 mL, stirring rate at 550 rpm, and solidifying time of 12 h. Under the optimum conditions, the size of the NPs was about 170 nm. In scale-up preparation experiments, the vacuum rotary evaporation of 6 h and the Tangential flow ultrafiltration (TFU) method were the optimum conditions. The results suggested that DDAB/PLA NPs exhibited a uniform particle size distribution, with an average size of 150.3 ± 10.4 nm and a narrow polydispersity index (PDI) of 0.090 ± 0.13, coupled with a high antigen loading capacity of 85.4 ± 4.0%. In addition, the DDAB/PLA NPs can be stored stably for 30 days and do not have side effects caused by residual solvents. For biosafety, the acute toxicity experiments showed good tolerance of the vaccine formulation even at a high adjuvant dose. The local irritation experiment demonstrated the reversibility of muscular irritation, and the repeated toxicity experiment revealed no significant necrosis or severe lesions in mice injected with the high-dose vaccine formulation. Overall, the DDAB/PLA NPs exhibit potential for clinical translation as a safe candidate vaccine adjuvant.