A self-assembling nanoparticle: Implications for the development of thermostable vaccine candidates

Liu, Ze-Hui; Xu, Huiling; Han, Guangwei; Tao, Li-Na; Lü, Ying; Zheng, Suya; Fang, Weihuan; He, Fang

doi:10.1016/j.ijbiomac.2021.06.024

Cited by 14 publications

(21 citation statements)

References 61 publications

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“…Highly purified BM-DCs were prepared from mice. 40 , 41 Using this model, we found that DCbp3 exhibited a distinctly higher targeting efficiency, and Cap-DCbp3 VLPs were efficiently internalized by BM-DCs and mainly located in the cytoplasm. It is well accepted that, upon exposure to microbial stimuli or Ags, immature DCs phagocytose Ags and undergo a maturation process characterized by the increased expression of co-stimulatory molecules, the production of pro-inflammatory cytokines and the presentation of Ags to T cells.…”

Section: Discussionmentioning

confidence: 93%

Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo

Lü

Liu

et al. 2022

IJN

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Background Dendritic cell (DC) targeted antigen delivery is a promising strategy to enhance vaccine efficacy and delivery of therapeutics. Self-assembling peptide-based nanoparticles and virus-like particles (VLPs) have attracted extensive interest as non-replicating vectors for nanovaccine design, based on their unique properties, including molecular specificity, biodegradability and biocompatibility. DCs are specialized antigen-presenting cells involved in antigen capture, processing, and presentation to initiate adaptive immune responses. Using DC-specific ligands for targeted delivery of antigens to DCs may be utilized as a promising strategy to drive efficient and strong immune responses. Methods In this study, several candidates for DC-binding peptides (DCbps) were individually integrated into C-terminal of porcine circovirus type 2 (PCV2) Cap, a viral protein that could self-assemble into icosahedral VLPs with 60 subunits. The immunostimulatory adjuvant activity of DC-targeted VLPs was further evaluated in a vaccine model of PCV2 Cap. Results With transmission electron microscopy (TEM), E. coli expressed Cap-DCbp fusion proteins were observed self-assembled into highly ordered VLPs. Further, in dynamic light scattering (DLS) analysis, chimeric VLPs exhibited similar particle size uniformity and narrow size distribution as compared to wild type Cap VLPs. With a distinctly higher targeting efficiency, DCbp3 integrated Cap VLPs (Cap-DCbp3) displayed enhanced antigen uptake and increased elicitation of antigen presentation-related factors in BM-DCs. Mice subcutaneously immunized with Cap-DCbp3 VLPs exhibited significantly higher levels of Cap-specific antibodies, neutralizing antibodies and intracellular cytokines than those with other DCbp integrated or wild type Cap VLPs without any DCbp. Interestingly, Cap-DCbp3 VLPs vaccine induces robust cellular immune response profile, including the efficient production of IFN-γ, IL-2 and IL-10. Meanwhile, the improved proliferation index in lymphocytes with Cap-DCbp3 was also detected as compared to other VLPs. Conclusion This study described the potential of DC-binding peptides for further improved antigen delivery and vaccine efficacy, explainning nanovaccine optimization in relation to a range of emerging and circulating infectious pathogens.

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Section: Discussionmentioning

confidence: 93%

Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo

Lü

Liu

et al. 2022

IJN

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“…Bacteria were cultured, treated with 0.06 mM isopropyl thiogalactoside (IPTG, Sangon, China), collected, suspended and lysed by ultrasonication. Then, supernatants containing the target proteins were collected and mixed with agarose resin (Yeasen, China), and target proteins were eluted with PBS supplemented with 500 mM imidazole (Liu et al, 2021 ). For the subsequent experiments, the purified proteins were analyzed by SDS–PAGE and Western blotting.…”

Section: Methodsmentioning

confidence: 99%

“…Purified Cap-tFlic fusion proteins were filtered and dialyzed at 16 °C overnight as described previously (Liu et al, 2021 ). VLPs were visualized by transmission electron microscopy (TEM, JEOL, JEM-1010) using 2% phosphotungstic acid (PTA, Aladdin, China) (pH 6.8) negative staining.…”

Section: Methodsmentioning

confidence: 99%

“…BM-DCs were isolated and cultured as described previously (Liu et al, 2021 ). Briefly, C576BL male mice were euthanized and dissected, and bone marrow-derived dendritic cells were resuspended and seeded in 6-well cell plates at a density of 10 6 cells/well.…”

Section: Methodsmentioning

confidence: 99%

“…Internalization of Cap VLPs by BM-DCs was measured as described previously (Liu et al, 2021 ). In brief, 100 μg/mL Cap VLPs and Cap-tFlic VLPs were added to cell cultures and incubated for 12 h. The cells were fixed with cold acetone, blocked with FBS, incubated with an anti-Cap monoclonal antibody (8C3), which was previously identified by this laboratory, for 1 h, and incubated with a fluorescent secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

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The truncated form of flagellin (tFlic) provides the 2dCap subunit vaccine with better immunogenicity and protective effects in mice

Lü

Liu

et al. 2022

Animal Diseases

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Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated diseases, and it causes substantial economic losses in the swine industry each year. It is crucial to develop an effective vaccine against the circulating strain PCV2d, which is prone to substantial degrees of mutation. In this study, a truncated form of flagellin (tFlic: 85-111 aa) was inserted into the C-terminal sequence of 2dCap, and Western blotting results showed that recombinant Cap-tFlic VLPs were successfully expressed. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) data indicated that purified recombinant Cap-tFlic fusion proteins existed in the form of polymers and that tFlic could not affect the formation and internalization of VLPs. Integrated Cap-tFlic VLPs induced the expression of antigen presentation-related factors (MHC-II and CD86) by bone marrow-derived dendritic cells (BM-DCs), and the expression of TLR5-related factors (TNF-α) was dramatically elevated. Mice intramuscularly immunized with Cap-tFlic VLPs exhibited significantly higher levels of Cap-specific antibodies and neutralizing antibodies than mice immunized with wild-type Cap VLPs. The data obtained in the current study indicate that Cap-tFlic may be a candidate for a subunit vaccine against PCV2 in the future.

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Nanoparticle and virus-like particle vaccine approaches against SARS-CoV-2

Kim

Seo

2022

J Microbiol.

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The global spread of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has provoked an urgent need for prophylactic measures. Several innovative vaccine platforms have been introduced and billions of vaccine doses have been administered worldwide. To enable the creation of safer and more effective vaccines, additional platforms are under development. These include the use of nanoparticle (NP) and virus-like particle (VLP) technology. NP vaccines utilize self-assembling scaffold structures designed to load the entire spike protein or receptor-binding domain of SARS-CoV-2 in a trimeric configuration. In contrast, VLP vaccines are genetically modified recombinant viruses that are considered safe, as they are generally replication-defective. Furthermore, VLPs have indigenous immunogenic potential due to their microbial origin. Importantly, NP and VLP vaccines have shown stronger immunogenicity with greater protection by mimicking the physicochemical characteristics of SARS-CoV-2. The study of NPand VLP-based coronavirus vaccines will help ensure the development of rapid-response technology against SARS-CoV-2 variants and future coronavirus pandemics.

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A self-assembling nanoparticle: Implications for the development of thermostable vaccine candidates

Cited by 14 publications

References 61 publications

Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo

Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo

The truncated form of flagellin (tFlic) provides the 2dCap subunit vaccine with better immunogenicity and protective effects in mice

Nanoparticle and virus-like particle vaccine approaches against SARS-CoV-2

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