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MSR–PEI vaccine enhances DC activation and trafficking in situ a, Schematic representations of the MSR vaccine (V), boxed in black, and MSR–PEI vaccine (VP), boxed in red. b, Total cell number at the vaccine site explanted on day 3 after immunization with V or VP using B60K PEI (n = 4, two-tailed t-test). c–e, Total number of CD11c⁺ CD86⁺ activated DCs (n = 4, two-tailed t-test) (c), CD11c⁺ CCR7⁺ LN homing DCs (n = 4, two-tailed t-test) (d) and SIINFEKL-presenting DCs (n = 4, two-tailed t-test) (e) recruited to the vaccine site on day 3 after immunization with V or VP using B60K PEI. f–h, Total number of cells (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (f), of CD11c⁺ CD86⁺ or CD11c⁺ MHC-II⁺ activated DCs (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (g) and OVA⁺ DCs (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (h) in the dLN on days 3 and 5 after immunization with V or VP using B60K PEI or left unimmunized (N). i, Schematic representations of the MSR–PEI trans vaccine (trans VP) and the MSR–PEI cis vaccine (cis VP). j, Total number of CD11c⁺ CD86⁺ activated DCs at the vaccine site on day 3 after immunization with the trans VP vaccine or the cis VP vaccine (n = 5, two-tailed t-test). k,l, Total number of CD11c⁺ CD86⁺ activated DCs (k) and CD11c⁺ OVA⁺ DCs (l) in the dLN on day 5 after immunization with the trans VP vaccine or the cis VP vaccine (n = 5, two-tailed t-test). Data depict mean ± s.d.
Source publication
Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhan...
Citations
... The self-adjuvated nanofiber vaccines were fabricated by coating Salmonella-derived flagella with cationic polyethyleneimine (PEI) and the model antigen of OVA through a layer-by-layer selfassembly nanotechnology. [26] Flagella obtained from VNP20009 (termed as FLA) were isolated and purified from its culture medium by a set of procedures including acidification, salting out, and ultracentrifugation ( Figure S1, Supporting Information). By simply mixing with negatively-charged FLA, positivelycharged PEI could be deposited onto flagellum surface via electrostatic interaction. ...
Bacteria‐based vaccines have received increasing attention given the ability to induce strong systemic immune responses. However, the application of bacteria as therapeutic agents inevitably suffers from infection‐associated side effects due to the living characteristics. Here, the use of bacteria‐derived flagella is described to construct self‐adjuvated nanofiber vaccines. With the help of charge‐reversal mediated by decoration with cationic polymers, the flagella can be coated with negatively charged antigens through electrostatic interaction. By virtue of the large aspect ratio, the resulting nanofiber vaccines show prolonged retention at the injection site and increased uptake by dendritic cells and macrophages. Thanks to the innate immunogenicity, self‐adjuvated flagella robustly promote dendritic cell maturation and macrophage polarization, resulting in the elicitation of antigen‐specific T‐cell and B‐cell immune responses. In ovalbumin‐overexpressing melanoma‐bearing mice, immunization with ovalbumin‐carried vaccines not only exhibits a favorable tolerance, but also displays superior inhibition efficacies on tumor growth and metastasis separately under the therapeutic and prophylactic settings. The flexibility of this approach is further demonstrated for vaccine fabrication by coating with the SARS‐CoV‐2 Spike protein S1 subunit. Bacterial flagella‐based self‐adjuvated nanofiber platform proposes a versatile strategy to develop various vaccines for disease prevention and treatment.
... Although subunit vaccines have great potential in cancer immunotherapy, the efficiency of antigen and adjuvants combined delivery to lymph nodes (LNs) is relatively low, 2,3 leading to weak immune stimulation and tolerance. In addition, in order to effectively induce CTLs mediated cellular immunity, antigens must enter APCs and then combine with major histocompatibility complex for synergistically activating APCs; 11,12 3) nanocarriers with small size increasing the aggregation of antigens in LNs, 13 further enhancing the immune response. ...
... This reaction mainly includes three important factors: 1) spatiotemporal control of antigen delivery to LNs; 25,34,35 2) cytoplasmic delivery and cross presentation of antigen in APCs; [36][37][38] 3) combined delivery of antigens and adjuvants. 11,12 The OVA@MMSNs@BM-Man nanovaccine meets the requirements of the above three factors. The prepared OVA@MMSNs@BM-Man nanovaccine can target DCs in LNs through the combination of mannose with CD205. ...
Introduction
Tumor vaccines can activate tumor-specific immune responses to inhibit tumor growth, recurrence, and metastasis. However, the efficiency of antigen and adjuvants combined delivery to lymph nodes (LNs) is relatively low, leading to weak immune stimulation and tolerance. In this study, a tumor nanovaccine was constructed for the targeted dendritic cells (DCs)-mediated immunotherapy.
Methods
Ovalbumin (OVA) antigen was first loaded into manganese-doped mesoporous silica nanoparticles (MMSNs) and coated with bacterial cytoplasmic membrane (BM), which was further inserted with mannose to prepare OVA@MMSNs@BM-Man nanovaccines. In vitro and in vivo experiments were conducted to assess their properties and function of the synthesized nanovaccines.
Results
The nanovaccine can effectively target DCs in LNs by the combination of mannose with mannose receptor (CD205). BM serves as an immune adjuvant and co-delivers with OVA antigen, effectively improving antigen presentation efficiency. In an acidic environment, the Mn²⁺ produced by the degradation of MMSNs can not only serve as an MR imaging agent but also activate the cGAS-STING pathway, followed by the release of IFN-β. The activated DCs further activate the body’s cytotoxic T cells (CTLs), thereby exerting anti-tumor effects.
The conclusion
This study will provide a new idea for the construction of tumor nanovaccines.
... Wild-type B16F10 cells were used to construct the tumour model. A mixture of mutation-derived neoantigen peptides (B16-M27, B16-M30, B16-M47 and B16-M48) were used to prepare various vaccines 54 . XMVs encapsulating B16 neoantigen peptides (XMV-B16), AUVs encapsulating B16 neoantigen peptides (AUV-B16), LIPs encapsulating B16 neoantigen peptides (LIP-B16) or free B16 neoantigen peptides (Free B16) were s.c. ...
Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA–lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans.
... Various nanomaterials have been used as delivery systems to improve the stability of TSAs. Polyethyleneimine-coated silica microrods can augment the immunogenicity of HPV-16 E7 and several peptides carrying novel antigens, with remarkable efficacy in tumor treatment in murine models [26]. Furthermore, conventional nanovaccine delivery systems often rely on nanocarriers, which can impede the effective delivery of new antigens and potentially result in significant toxicity. ...
Tumor vaccines have become a crucial strategy in cancer immunotherapy. Challenges of traditional tumor vaccines include inadequate immune activation and low efficacy of antigen delivery. Nanoparticles, with their tunable properties and versatile functionalities, have redefined the landscape of tumor vaccine design. In this review, we outline the multifaceted roles of nanoparticles in tumor vaccines, ranging from their capacity as delivery vehicles to their function as immunomodulatory adjuvants capable of stimulating anti-tumor immunity. We discuss how this innovative approach significantly boosts antigen presentation by leveraging tailored nanoparticles that facilitate efficient uptake by antigen-presenting cells. These nanoparticles have been meticulously designed to overcome biological barriers, ensuring optimal delivery to lymph nodes and effective interaction with the immune system. Overall, this review highlights the transformative power of nanotechnology in redefining the principles of tumor vaccines. The intent is to inform more efficacious and precise cancer im-munotherapies. The integration of these advanced nanotechnological strategies should unlock new frontiers in tumor vaccine development, enhancing their potential to elicit robust and durable anti-tumor immunity.
... [1,2] Welldesigned multifunctional nanovaccines can improve immune responses by enhancing various dimensions of immune activation pathways, such as boosting cellular uptake, [3,4] targeting antigen-presenting cells (APCs) or the lymphatic system, [3] or enhancing escape from endosomes. [5] However, current nanovaccine technologies rely on chemical or hybrid semibiological synthesis methods, [6,7] which significantly limit production efficiency. In contrast, engineered bacteria and mammalian cells can achieve complete protein biosynthesis. ...
Nanovaccines have significantly contributed in the prevention and treatment of diseases. However, most of these technologies rely on chemical or hybrid semibiological synthesis methods, which limit the manufacturing performance advantages and improved inoculation outcomes compared with traditional vaccines. Herein, a universal and purely biological nanovaccine system is reported. This system integrates three modules: (1) self‐assembling nanoparticles, (2) self‐catalyzed synthesis of small‐molecule stimulator of interferon gene (STING) agonists, and (3) delivery vectors that target the cytosolic surveillance system. Various nanoparticles are efficiently self‐assembled using this system. After confirming the excellent immunostimulatory and lymph node targeting of this system, its broad‐spectrum antiviral efficacy is further demonstrated. By leveraging the comprehensive biosynthetic capabilities of bacterial cells, this system can efficiently combine various adjuvant‐active modular components and antigenic cargo, thereby providing a highly diversified and potent vaccine platform.
... In pursuit of fine-tuning antibody production within humoral immunity, the focus has shifted to targeting B cells using biomaterials as carriers for biologic antigens (vaccines), notably in the form of micro-and nano-particles. This strategy aims to address a range of diseases, such as infections, autoimmune disorders, and cancer [136][137][138]. When considering humoral immunity from ECM-based biomaterials, some molecules possibly considered as antigen types are released during biomaterial implantation in tissue. ...
Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.
... Designing a nanoparticle-based vaccine that combines the characteristics of nanoparticles and tumor vaccines to achieve personalized and precise treatment has become the current and future trend. To achieve personalization, predecessors have tried to improve the tumor immunogenicity, such as using polyethyleneimine (PEI) to enhance the immunogenicity of antigens in mesoporous silica rods (MSR) vaccines (97), or using neoantigens in combination with other immune interventions. In addition, the tumor immune microenvironment is dynamic and changes over the course of treatment, necessitating the development of personalized, stagespecific intervention techniques based on different immune treatment stages. ...
Background
Nanovaccine treatment is an exciting area of research in immunology and personalized medicine, holding great promise for enhancing immune responses and targeting specific diseases. Their small size allows efficient uptake by immune cells, leading to robust immune activation. They can incorporate immune-stimulating molecules to boost vaccine efficacy. Therefore, nanovaccine can be personalized to target tumor-specific antigens, activating the immune system against cancer cells. Currently, there have been ample evidence showing the effectiveness and potential of nanovaccine as a treatment for cancer. However, there was rare bibliometric analysis of nanovaccine for cancer. Here we performed a bibliometric and visual analysis of published studies related to nanovaccine treatment for cancer, providing the trend of future development of nanovaccine.
Methods
We collected the literatures based on the Web of Science Core Collection SCI-Expanded database. The bibliometric analysis was performed via utilizing visualization analysis tools VOSviewer, Co-Occurrence (COOC), Citespace, Bibliometrix (R-Tool of R-Studio), and HitCite.
Results
A total of 517 literatures were included in this study. China is the country with the most publications and the highest total local citation score (TLCS). The Chinese Academy of Sciences holds the largest research count in this field and the most prolific author is Deling Kong from Nankai University. The most prominent journal for publishing in this area is Biomaterials. The researches mainly focus on the therapeutic process of tumor nanovaccines, the particle composition and the application of nanovaccines, suggesting the potential hotspots and trends of nanovaccine.
Conclusion
In this study, we summarized the characteristics and variation trends of publications involved in nanovaccine, and categorized the most influential countries, institutions, authors, journals, hotspots and trends regarding the nanovaccine for cancer. With the continuous development of nanomaterials and tumor immunotherapy, nanovaccine for cancer provides a research field of significant clinical value and potential application.
... The RPKM calculation for a gene is determined by the formula: RPKM = 1 × 10 9 × (total exon reads)/ (mapped reads (millions) × exon length (bp) [24]. Then, the immunogenicity of different CT26 neoepitopes related to the selected highly-expressed gene was assessed based on different in vitro and in vivo studies [22,[25][26][27]. ...
... Based on the experimental data [22,23,27], 25 CT26 neoepitopes were first selected according to gene expression (RPKM) value, IFN-γ enzyme-linked immunospot (ELISpot) score, prevention of lung metastasis, and inhibition of tumor growth (Table 1). It was found that a threshold RPKM value of 0.3 can effectively balance the occurrence of false positives and false negatives [52]. ...
... We also performed a strategy combining previous in vitro and in vivo results as well as in silico approaches to select the best CT26 neoepitopes. In the first step of the current study, seven CT26 neoepitopes were selected based on previous studies on common neoantigens of CT26 and their evaluation criteria, including RPKM, IFN-ELISpot score, reduction of tumor development, and prevention of lung metastasis [27] (Table 1). To select the final neoepitopes of our construct, the high-ranked MHC-I binding (Table 2), CTL epitopes (Table 3), MHC-II binding (Table 4) (Table 5) of CT26 neoepitopes were in silico evaluated. ...
Simultaneous targeting of several mutations can be useful in colorectal cancer (CRC) due to its heterogeneity and presence of somatic mutations. As CT26 mutations and expression profiles resemble those of human CRC, we focused on designing a polyepitope vaccine based on CT26 neoepitopes. Due to its low immunogenicity, outer membrane vesicles (rOMV) as an antigen delivery system and adjuvant was applied. Herein, based on previous experimental and our in silico studies four CT26 neoepitopes with the ability to bind MHC-I and MHC-II, TCR, and induce IFN-α production were selected. To increase their immunogenicity, the gp70 and PADRE epitopes were added. The order of the neoepitopes was determined through 3D structure analysis using ProSA, Verify 3D, ERRAT, and Ramachandran servers. The stable peptide-protein docking between the selected epitopes and MHC alleles strengthen our prediction. The CT26 polytope vaccine sequence was fused to the C-terminal of cytolysin A (ClyA) anchor protein and rOMVs were isolated from endotoxin-free ClearColi™ strain. The results of the C-ImmSim server showed that the ClyA-CT26 polytope vaccine could induce T and B cells immunity.The ClyA-CT26 polytope was characterized as a soluble, stable, immunogen, and non-allergen vaccine and optimized for expression in ClearColi™ 24 h after induction with 1 mM IPTG at 25 °C. Western blot analysis confirmed the expression of ClyA-CT26 polytope by ClearColi™ and also on ClearColi™-derived rOMVs. In conclusion, we found that ClearColi™-derived rOMVs with CT26 polytope can deliver CRC neoantigens and induce antitumor immunity, but in vivo immunological studies are needed to confirm vaccine efficacy.
... Moreover, bioengineered therapies can be personalized based on a patient's unique genetic profile and tumor characteristics, increasing treatment effectiveness. [91] On this basis, bioengineered OMVs have been explored as a novel platform for cancer therapy. Bioengineered OMVs encompass two approaches: OMVs produced by engineered bacteria and directly modified isolated OMVs. ...
In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria‐derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state‐of‐the‐art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.
... In addition, nanomaterials not only serve as delivery vehicles for pyroptosis initiators but also as immune adjuvants to help activate immune responses. Recent studies have found that some nanomaterials such as PEI, 169 pH-sensitive polymer bearing a seven-membered ring with a tertiary amine (PC7A), 170 poly(D-lactic acid) nanoparticles, 171 and chiral polypeptide nanoparticles 172 evoke cellular or humoral immune responses. The underlying mechanism of nanoadjuvants may be related to the activation of toll-like receptors or stimulator of interferon genes pathways. ...
Pyroptosis, a pro-inflammatory and lytic programmed cell death pathway, possesses great potential for antitumor immunotherapy. By releasing cellular contents and a large number of pro-inflammatory factors, tumor cell pyroptosis can promote dendritic cell maturation, increase the intratumoral infiltration of cytotoxic T cells and natural killer cells, and reduce the number of immunosuppressive cells within the tumor. However, the efficient induction of pyroptosis and prevention of damage to normal tissues or cells is an urgent concern to be addressed. Recently, a wide variety of nanoplatforms have been designed to precisely trigger pyroptosis and activate the antitumor immune responses. This review provides an update on the progress in nanotechnology for enhancing pyroptosis-based tumor immunotherapy. Nanomaterials have shown great advantages in triggering pyroptosis by delivering pyroptosis initiators to tumors, increasing oxidative stress in tumor cells, and inducing intracellular osmotic pressure changes or ion imbalances. In addition, the challenges and future perspectives in this field are proposed to advance the clinical translation of pyroptosis-inducing nanomedicines.
