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adjuvants (ImmuMax / ImmuMax SR / adjuvants, Repros)

✓ Approved

Repros Therapeutics Inc. · 小分子 · 小分子

什么是 adjuvants？

adjuvants 是一种小分子，由Repros Therapeutics Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Unknown。

药物档案

商品名ImmuMax, ImmuMax SR, adjuvants, Repros
公司Repros Therapeutics Inc.
药物类别小分子
给药途径Unknown
状态Approved
来源： ClinicalTrials.gov, Repros Therapeutics Inc.

治疗适应症

adjuvants 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Surgical and medical proceduresOral appliance application✓ Approved

相关研究文献

PubMedNature communications2026-06-13

Efficacy of Pam3CSK4 as a cross-species adjuvant for polysaccharide vaccines in humanized mouse and non-human primate models.

Jennings-Gee Jamie E JE, Adams-Sims Alexis E AE, Haas Karen M KM

Polysaccharide-based vaccines are essential for preventing bacterial infections, but their effectiveness is limited by weak antibody responses and lack of suitable adjuvants. TLR4 agonists enhance polysaccharide-specific antibody responses through B cell-intrinsic TLR4-MyD88 signaling in mice, but this mechanism is not conserved in primates, prompting the search for alternative MyD88-activating agonists. In vitro, the TLR1/2 agonist Pam3CSK4 synergizes with strong BCR crosslinking to enhance activation and antibody secretion by mouse and human B cells. In vivo, Pam3CSK4 in squalene emulsion increases protective pneumococcal polysaccharide-specific antibody responses in both immunocompetent and humanized mice. Although a dual TLR2/7 agonist shows strong in vitro activity, it fails to enhance polysaccharide-specific IgG responses in vivo, consistent with antagonism observed when Pam3CSK4 and TLR7 agonists are combined. In contrast, incorporating Pam3CSK4 into an adjuvant containing a TLR4 agonist, synthetic cord factor, and squalene emulsion further enhances memory B cell generation and protective antibody responses in mice and restores adjuvant activity in non-human primates, supporting Pam3CSK4-based formulations as promising adjuvants for polysaccharide vaccines.

PMID 42285953
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PubMedInternational immunopharmacology2026-06-13

Neoantigen-based multi-epitope vaccine designing against glioblastoma using reverse vaccinology and immunoinformatic approaches.

Din Miraj Ud MU, Ahmad Sajjad S, Liu Xiaohui X, Jiang Hui H et al.

One of the primary factors in the development of cancer is the accumulation of genetic mutations. Some of these genetic mutations result in the emergence of unique antigens called neoantigens. These neoantigens are perceived as non-self by T cells, making them prime targets for cancer vaccines. These neoantigen-based vaccines can elicit a promising immune response against the malignant cells. In the current research work, a computational approach was employed to design a multi-epitope vaccine for glioblastoma. A set of 126 neoantigens was retrieved from the CEDAR cancer epitopes database which yielded 446 epitopes. The epitopes were screened and 10 potential epitopes were selected to design a multi-epitope vaccine. GPGPG linkers were used for combining these epitopes, while adjuvants were connected to the vaccine via EAAAK and RVRR linkers to build the final construct of the vaccine. The physicochemical properties of the vaccine indicated that the designed vaccine is highly antigenic (0.7841 antigenicity score), non-allergenic, non-toxic, and also water soluble. Molecular docking assessed the interaction of the vaccine with MHC-I, MHC-II, and TLR-4, demonstrating strong binding affinities (-886.5 kcal/Mol, -1050.2 kcal/Mol, and - 1018.3 kcal/Mol, respectively). The docking results were further supported by the normal mode analysis and molecular dynamics simulation showing average RMSD values of 4.21 Å, 6.80 Å, and 5.68 Å for the three complexes, respectively. The in silico cloning of the vaccine into the bacterial plasmid (pET28a+) was carried out to enhance its expression achieving a GC content of 57.43 and a codon adaptation index of 1. The in silico immune simulation revealed that peak antigen levels (∼7.5 × 105 counts/mL at approximately day 50) elicited strong humoral and cellular immune responses, characterized by elevated IgM + IgG titers (∼2.8 × 105) and increased cytokine production, including IFN-γ (∼4.5 × 105), IL-2 (∼6.0 × 105), and TNF-α (∼1.2 × 105 ng/mL), indicating robust immune activation. These findings indicated that our designed vaccine could be a potential therapeutic candidate against glioblastoma. Further experimental research is required to validate the potential, efficacy, and safety of the designed vaccine.

PMID 42284765
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PubMedJournal of clinical medicine2026-06-12

Intrathecal Nalbuphine Versus Other Opioids as Adjuvant to 0.5% Hyperbaric Bupivacaine in Caesarean Section: A Systematic Review and Meta-Analysis.

Theodorou-Kanakari Anna A, Karathanasi Styliani S, Lykoudis Panagis M PM, Rekatsina Martina M et al.

Background/Objectives: Subarachnoid anaesthesia is widely preferred for caesarean delivery due to its rapid onset, reliability, and safety. The addition of adjuvants to intrathecal hyperbaric bupivacaine has been shown to enhance the quality of anaesthesia and prolong postoperative analgesia. Opioids are among the most frequently used intrathecal adjuvants; however, their administration is associated with adverse effects. Nalbuphine, a mixed opioid agonist-antagonist, may be a promising agent for obstetric use due to its favourable pharmacodynamic properties. This study aimed to systematically review and, where feasible, meta-analyse the evidence comparing nalbuphine with other intrathecal opioid adjuvants to hyperbaric bupivacaine 0.5% for caesarean section, with a primary focus on efficacy and safety. Methods: A systematic review and meta-analysis of controlled trials was conducted. Web of Science Core Collection, MEDLINE (PubMed), Scopus, the Library of Congress, and LISTA (EBSCO) were systematically searched to identify eligible studies. Pooled mean difference (MD) and risk ratio (RR) were calculated using random-effects model. Results: Ten studies encompassing 1095 parturients were included. Compared with fentanyl, intrathecal nalbuphine was associated with a modest prolongation of effective analgesia. However, this finding was accompanied by substantial heterogeneity and very low certainty of evidence. In contrast, morphine provided a longer duration of analgesia than nalbuphine. Overall, nalbuphine and fentanyl demonstrated comparable block characteristics, with only minimal and clinically insignificant differences in onset and duration. Importantly, nalbuphine was associated with fewer adverse effects, particularly shivering and PONV. Conclusions: Subarachnoid nalbuphine may serve as a potential alternative adjuvant to 0.5% hyperbaric bupivacaine in caesarean section anaesthesia. It may provide an analgesic efficacy comparable to fentanyl and, although less potent than morphine, it may demonstrate a more favourable safety profile.

PMID 42278974
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PubMedRSC pharmaceutics2026-06-12

Dual-adjuvant mucosal vaccine leveraging mast cell and TLR9 agonists for protection against poxvirus infection.

Murphy Connor T CT, Williamson Grace L GL, Ontiveros-Padilla Luis L, Hendricksen Aaron T AT et al.

Mast cells (MC) are innate immune cells that are predominantly localized under the skin and at mucosal surfaces, and play a role in numerous physiological processes, including host response to pathogens. Recently, mast cell activators (MCA) have been identified as mucosal vaccine adjuvants that are able to promote a strong and antigen-specific immune response. We performed an extensive structure-activity relationship (SAR) analysis on the previously identified small molecule MCA, ST101036, to further optimize its adjuvanticity. This led to the development of the derivative, VAP-1185, which demonstrated improved mast cell degranulation activity in vitro, and a Th2-biased in vivo immune response. While mucosal vaccines with a single adjuvant have shown effectiveness, combining two adjuvants can activate multiple immune pathways, leading to a stronger and more comprehensive immune response. Additionally, dual adjuvant vaccines can elicit a balanced Th1/Th2 response, leading to equally effective cellular and humoral responses. We combined VAP-1185 with the FDA-approved adjuvant, cytosine phosphoguanine (CpG), which activates toll-like receptor 9 (TLR9) and promotes a Th1-biased immune response. This dual adjuvant formulation promotes inflammatory cytokine production in vitro, additive humoral effects and an active cellular response in vivo, as well as a favorable safety profile when intranasally administered to C57BL/6 mice. Subsequently, this adjuvant formulation was also able to confer protection against a lethal challenge of vaccinia virus in BALB/c mice. Thus, we report a novel mucosal vaccine formulation that produces an effective Th1/Th2 balanced immune response.

PMID 42283057
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PubMedApplied and environmental microbiology2026-06-12

Xylose-induced tricarboxylic acid cycle activation resensitizes gentamicin-resistant Escherichia coli.

Chen Ling L, Kuang Sufang S, Bao Chenyu C, Fu Wenjing W et al.

The escalating antibiotic resistance crisis requires innovative strategies to revitalize existing antibiotics. Here, we report that xylose, a food-grade sugar poorly metabolized by humans but readily utilized by bacteria, acts as a potent metabolic adjuvant to restore gentamicin efficacy against bacteria. Using a laboratory-evolved gentamicin-resistant E. coli strain, we showed that xylose enhances gentamicin-mediated killing in a dose- and time-dependent manner, achieving a 200-fold reduction in viability with a synergy score 25.25. This synergistic bactericidal effect was also confirmed in multidrug-resistant and carbapenem-resistant bacteria and a mouse infection model, boosting survival rates by 30%. Metabolomics and pathway analyses revealed that xylose induced a global metabolic shift, upregulating pyruvate and succinate as biomarkers and activating the tricarboxylic acid (TCA) cycle. Exogenous addition of pyruvate and succinate also contributed to the bactericidal effect of gentamicin. This is accompanied by increased activity of key TCA enzymes (PDH, α-KGDH, SDH, MDH), elevated NADH and ATP levels, and enhanced proton motive force (PMF). However, when TCA cycle enzymes α-ketoglutarate dehydrogenase or succinate dehydrogenase were inhibited via gene knockout or sodium malonate, or when PMF was dissipated by carbonyl cyanide m-chlorophenylhydrazone (CCCP), the synergistic bactericidal effect was abolished. Xylose treatment increased intracellular gentamicin accumulation by 2.34-fold, an effect that was also blocked by TCA cycle or PMF inhibition. Our study established xylose as a bacteria-selective adjuvant that revitalizes gentamicin by reactivating TCA cycle dependent drug uptake, offering a potential strategy to combat antibiotic resistance.IMPORTANCEThis work provided a critical advance in the fight against antibiotic resistance by transforming a common food-grade sugar into a targeted therapeutic tool. Unlike conventional antibiotics or previously reported adjuvants, xylose is uniquely selective: it is efficiently utilized by bacteria but poorly metabolized in humans, thereby minimizing off-target effects. We demonstrated for the first time that xylose reversed resistance by reactivating the silenced TCA cycle in resistant bacteria, going beyond mere substrate provision to restore a critical metabolic function. This mechanism not only revitalized the efficacy of gentamicin but also established a new strategy, exploiting the metabolic differences between host and pathogen to develop "pathogen-focused" adjuvants.

PMID 42283631
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PubMedbioRxiv : the preprint server for biology2026-06-12

Atomic layer deposition for core-shell microparticle vaccines enabling programmable antigen delivery to lymph nodes enhance humoral immune responses.

Chaudhary Namit N, Coleman Holly J HJ, Paolone Elias V EV, Yu Jiancheng J et al.

Technologies that simplify complex dosing regimens as single-shot immunizations may be important for vaccines against difficult to neutralize pathogens. Here we characterized delivery mechanism of clinically-relevant HIV vaccine immunogens using core-shell microparticles comprising immunogen formulations spray-dried to form solid spherical microparticles and subsequently coated with a nanoscopic alumina shell using atomic layer deposition (ALD). ALD particles exhibited a time delay in antigen release programmed by the alumina shell followed by prolonged antigen release, which steadily accumulated in antigen-presenting cells at the injection site and draining lymph nodes and accumulated on follicular dendritic cells in B cell follicles. ALD vaccines elicited continuous expansion of antigen-specific germinal center B cells over 8 weeks, serum antibody responses with >10-fold slower antigen-binding off-rates, and 2-fold more long-lived plasma cells compared to traditional bolus vaccination with potent adjuvants. Single administration ALD technology thus promotes key events in the primary immune response important for vaccines against HIV and other challenging pathogens.

PMID 42282721
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