Polymerized Porin as a Novel Delivery Platform for Coronavirus Vaccine

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. Here, we designed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We use surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane in this study. More importantly, the polymerized RBD displayed on ClyA-RBD polymerized porin (RBD-PP) already has some correct spatial structures of virus spikes. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies and systemic cellular immune responses and immune memory. We applied ofthis PP-based vaccine platform to make an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to be applied to more fields, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.

Tumor Antigen-Based Nanovaccines for Cancer Immunotherapy: A Review

As an important means of tumor immunotherapy, tumor vaccines have achieved exciting results in the past few decades. However, there are still many obstacles that hinder tumor vaccines from achieving maximum efficacy, including lack of tumor antigens, low antigen immunogenicity and poor delivery efficiency. To overcome these challenges, researchers have developed and investigated various new types of tumor antigens with higher antigenic specificity and broader antigen spectrum, such as tumor-specific peptide antigens, tumor lysates, tumor cell membrane, tumor associated exosomes, etc. At the same time, different nanoparticulate delivery platforms have been developed to increase the immunogenicity of the tumor antigens, for example by increasing their targeting efficiency of antigen-presenting cells and lymph nodes, and by co-delivering antigens with adjuvants. In this review, we summarized different types of the tumor antigens that have been reported, and introduced several nanovaccine strategies for increasing the immunogenicity of tumor antigens. The review of recent progress in these fields may provide reference for the follow-up studies of tumor antigen-based cancer immunotherapy.

Aggregation-Induced Emission-Based Vaccine Improves Potential Antitumor Immunotherapy

Recently, immunomodulation based on biomaterials has held great promise for preventing and treating cancer. Tumor vaccination can be considered as one of promising immunotherapies, compared with the vaccines for infectious disease, it still stays in its infant. Herein, we designed a near-infrared-emitting AIEgens (named TPE-Ph-DCM) based vaccine as an adjuvant in enhancing immune response. AIE-based photodynamic vaccine exhibited efficiently enhancement of the DC?s antigen prestation and elicited antigen-specific cytotoxic T lymphocyte functionality, and significantly inhibited B16-OVA tumor growth prophylactically and therapeutically in mice model. This study is expected to provide a scientific basis for developing effective and safe tumor vaccines.

Identification of Tumor Antigens and Immune Landscape in Glioblastoma for mRNA Vaccine Development

Background: Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to the intrinsic radio- and chemo-resistance. As an essential part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against GBM remains undefined. Therefore, this study aims to find the possible tumor antigens of GBM and identify the suitable population for cancer vaccination through immunophenotyping.Method: The genomic and responding clinical data of 169 GBM samples and five normal brain samples were obtained from The Cancer Genome Atlas (TCGA). The mRNA_seq data of 940 normal brain tissue were downloaded from Genotype-Tissue Expression (GTEx). Potential GBM mRNA antigens were screened out by differential expression, copy number variant (CNV), and mutation analysis. K-M survival and Cox analysis were carried out to investigate the prognostic association of potential tumor antigens. Tumor Immune Estimation Resource (TIMER) was used to explore the association between the antigens and tumor immune infiltrating cells (TIICs). Immunophenotyping of 169 samples was performed through consensus clustering based on the abundance of 22 kinds of immune cells. The characteristics of the tumor immune microenvironment (TIME) in each cluster were explored through single-sample gene set enrichment analysis based on 29 kinds of immune-related hallmarks and pathways. Weighted gene co-expression network analysis (WGCNA) was performed to cluster the genes related to immune subtypes. Finally, pathway enrichment analyses were performed to annotate the potential function of modules screened through WGCNA.Results: Two potential tumor antigens selected were significantly positively associated with the antigen-presenting immune cells (APCs) in GBM. Furthermore, the expression of antigens was verified at the protein level by Immunohistochemistry. Two robust immune subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2), representing immune status “immune inhibition” and “immune inflamed”, respectively, had distinct clinical outcomes in GBM.Conclusion: ARPC1B and HK3 were potential mRNA antigens for developing GBM mRNA vaccination, and the patients in IS2 were considered the most suitable population for vaccination in GBM.

Application of Immunotherapy in Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the most common malignancies globally. It not only has a hidden onset but also progresses rapidly. Most HCC patients are already in the advanced stage of cancer when they are diagnosed, and have even lost the opportunity for surgical treatment. As an inflammation-related tumor, the immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy can activate tumor-specific immune responses, which brings a new hope for the treatment of HCC. At the present time, main immunotherapy strategies of HCC include immune checkpoint inhibitors, tumor vaccines, adoptive cell therapy, and so on. This article reviews the application and research progress of immune checkpoint inhibitors, tumor vaccines, and adoptive cell therapy in the treatment of HCC.

Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development

Background As an important part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against lower grade glioma (LGG) remains undefined. Immunophenotyping of tumors is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Therefore, this study aims to find the potential tumor antigen of LGG and identify the suitable population for cancer vaccination based on the immune landscape. Method The genomic and clinical data of 529 patients with LGG were obtained from TCGA, the mRNA_seq data of normal brain tissue were downloaded from GTEx. Differential expression gene and mutation analysis were performed to screen out potential antigens, K-M curves were carried out to investigate the correlation between the level of potential antigens and OS and DFS of patients. TIMER dataset was used to explore the correlation between genes and immune infiltrating cells. Immunophenotyping of 529 tumor samples was based on the single-sample gene sets enrichment analysis. Cibersort and Estimate algorithm were used to explore the tumor immune microenvironment characteristics in each immune subtype. Weighted gene co-expression network analysis (WGCNA) clustered immune-related genes and screened the hub genes, and pathway enrichment analyses were performed on the hub modules related to immune subtype in the WGCNA. Results Selecting for the mutated, up-regulated, prognosis- and immune-related genes, four potential tumor antigens were identified in LGG. They were also significantly positively associated with the antigen-presenting immune cells (APCs). Three robust immune subtypes, IS1, IS2 and IS3, represented immune status "desert", "immune inhibition", and "inflamed" respectively, which might serve as a predictive parameter. Subsequently, clinicopathological features, including the codeletion status of 1p19q, IDH mutation status, tumor mutation burden, tumor stemness, etc., were significantly different among subtypes. Conclusion FCGBP, FLNC, TLR7, and CSF2RA were potential antigens for developing cancer vaccination, and the patients in IS3 were considered the most suitable for vaccination in LGG.