A major challenge in the use of DNA vaccines is efficient delivery vivo. Establishing a safe and electric transfer method key to developing rapid against emerging infectious diseases. To overcome complexity designing new machines for delivery, clinically approved machine could be considered as an alternative. Here, we report electroacupuncture machine-based vaccine after intramuscular injection COVID-19 vaccine. The S gene SARS-CoV-2 pVAX1 plasmid (pSARS2-S) was used antigen this study. We...

Abstract Cross-presentation is a key function of dendritic cells (DCs), which present exogenous Ags on MHC class I molecules to prime CTL responses. The effects TLR triggering the cross-presentation by DCs remain unclear. In this study, we used synthetic dipalmitoylated peptides and TLR2 agonist–conjugated as models elucidate mechanisms TLR2-mediated cross-presentation. We observed that internalization bone marrow–derived was facilitated via clathrin-mediated endocytosis. administration...

DNA vaccines for infectious diseases and cancer have been explored years. To date, only one vaccine (ZyCoV-D) has authorized emergency use in India. are inexpensive long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success mRNA/lipid nanoparticle (LNP) technology coronavirus disease 2019 (COVID-19) pandemic opened a new application nucleic acid-based vaccines. Here, we report that plasmid encoding trimeric spike protein with LNP delivery...

Abstract The inhibitory effect of DAP12 on macrophages has been revealed by examining myeloid cells from DAP12‐deficient mice. In this report, we demonstrate that both and the FcϵRIγ‐chain (FcRγ) are required for negative regulation TLR responses in bone marrow‐derived dendritic (DC). Loss FcRγ enhanced pro‐inflammatory cytokine production maturation DC after stimulation, resulting a greater percentage produced IL‐12 p40, TNF, IL‐6, expressed high levels MHC class II, CD80, CD86. Whereas...

Dendritic cells (DC) play a central role in the initiation and regulation of immune responses. Increasing evidence has indicated that manipulation DC can serve as therapeutic mechanism for immunomodulation. In this study we tested some unique compounds isolated from Antrodia cinnamomea, medicinal fungus Taiwan, on mouse bone marrow-derived activation. A triterpenoid methyl antcinate K (me-AntK) promoted maturation by enhancing expression MHC class II, CD86, reducing endocytosis. TNF-alpha,...

The E7 oncoprotein of human papillomavirus (HPV) is an ideal target for developing immunotherapeutic strategies against HPV-associated tumors. However, because protein-based immunogens alone are poor elicitors the cytotoxic T-lymphocyte (CTL) responses, they have been difficult to exploit therapeutic purposes. In this study, we report that a recombinant lipoprotein consisting inactive (E7m) biologically linked bacterial lipid moiety (rlipo-E7m) induces maturation mouse bone marrow-derived...

The development of efficient vaccines against COVID-19 is an emergent need for global public health. spike protein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a major target the vaccine. To quickly respond to outbreak SARS-CoV-2 pandemic, nucleic acid-based vaccine novel option, beyond traditional inactivated virus or recombinant Here, we report DNA containing gene delivery via electroporation. genes SARS-CoV and were codon optimized mammalian cell expression then cloned...

Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or an electroporation device into muscle skin host. However, these systems come with certain obstacles, including limited transgene capacity, broad preexisting immunity in humans, and substantial cell death caused by high voltage pulses, respectively. In this study, we repurposed use amphiphilic bioresorbable copolymer (ABC), called PLA-PEG, as surface engineering agent that conciliates...

It has been reported that lipopeptides can be used to elicit cytotoxic T lymphocyte (CTL) responses against viral diseases and cancer. In our previous study, we determined mono-palmitoylated peptides enhance anti-tumor in the absence of adjuvant activity. To investigate whether di-palmitoylated with TLR2 agonist activity are able induce immunity, synthesized a di-palmitic acid-conjugated long peptide contains murine CTL epitope HPV E749–57 (Pam2IDG). Pam2IDG stimulated maturation bone...

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, involves a liable manufacturing process would be advantageous distribute around world. Here, we designed produced recombinant spike (S)-Trimer maintained in prefusion state exhibits high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20...

The inhibitory effect of DAP12 on macrophages has been revealed by examining myeloid cells from DAP12‐deficient mice. In this report, we demonstrate that both and the FcεRγ ‐chain (FcRγ) are required for negative regulation TLR responses in bone marrow‐derived dendritic (DCs). Loss FcRγ enhanced pro‐inflammatory cytokine production maturation DCs after stimulation, resulting a greater percentage produced IL‐12 p40, TNF, IL‐6, expressed high levels MHC class II, CD80, CD86. Whereas lacking...

Abstract The major challenge in COVID‐19 vaccine effectiveness is immune escape by SARS‐CoV‐2 variants. To overcome this, an Omicron‐specific messenger RNA (mRNA) was designed. extracellular domain of the spike Omicron variant fused with a modified GCN4 trimerization low immunogenicity (TSomi). After immunization TSomi mRNA hamsters, animals were challenged virus. raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and S. However, neutralized virus...

The tumor necrosis factor receptor associated protein 1 (TRAP1) is a mitochondria chaperon that has been previously implicated as target for cancer therapy due to its expression level linked progression. In this study, an immunodominant phosphopeptide of TRAP1 was identified from HLA-A2 gene transfected mouse cell line using mass spectrometry, and synthetic generated evaluate the potency on immunotherapy. transporter with antigen processing (TAP) deficient cell, conjugated phosphate group...

The major challenge of antitumor immunotherapy is dealing with the immunosuppressive tumor microenvironment, which involves immature myeloid cell accumulation that results in T dysfunction. Myeloid activation induced by Toll-like receptor agonists. Additionally, granulocyte/macrophage colony stimulating factor (GM-CSF) promotes myelopoiesis and recruits cells. Here, we combined 2 (TLR2) agonist lipoprotein GM-CSF to assess whether this bifunctional has synergistic effects on cells could be...

The induction of long-lived effector CD8+ T cells is key to the development efficient cancer vaccines. In this study, we demonstrated that a Toll-like receptor 2 (TLR2) agonist-fused antigen increased presentation via TLR2 signaling and induced memory-like against after immunization. N-terminus ovalbumin (OVA) was biologically fused with bacterial lipid moiety agonist produce recombinant lipidated (rlipo-OVA). We rlipo-OVA activated bone marrow-derived dendritic (BM-DCs) maturation by major...

Dendritic cells (DCs) are antigen-presenting involved in T cell activation and differentiation to regulate immune responses. Lipoimmunogens can be developed as pharmaceutical lipoproteins for cancer immunotherapy target DCs via toll-like receptor 2 (TLR2) signaling. Previously, we constructed a lipoimmunogen, lipidated human papillomavirus (HPV) E7 inactive mutant (rlipoE7m), inhibit the growth of HPV16 E7-expressing tumor murine model. Moreover, this antitumor effect could enhanced by...

Cross-presentation by DCs is the major mechanism which exogenous antigens activate CTLs. However, mechanisms of entry and presentation vaccine peptides remain unclear. In this study, we determined that antigen differed between nonlipidated monopalmitoylated peptide antigens. We found a long could be taken up colocalized with early endosomes. The uptake was inhibited at low temperatures or depolymerization actin filaments microtubules. contrast, lipidated were internalized temperatures,...

Peptide vaccines are safe, and aim to elicit expand tumor-specific immunity so as eradicate tumors. However, achieving strong long-lasting anti-tumor with peptide for the antigen-specific treatment of cancer is challenging, in part because their efficacy depends on adjuvants or immunomodulators. We approached this problem by conjugating an epitope-based vaccine a lipidated sequence (an immunomodulator) immune response. Lipidated non-lipidated polyepitope proteins were generated that...