In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses.

There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4+ T cells and CD8+ T cells. Vaccination with BP-OVA in the absence of adjuvant elicited antigen presentation to OVA-specific CD8+ and CD4+ T cells and cross-primed effective cytotoxic T lymphocyte (CTL) killers. BP-OVA induction of CTL killing did not require CD4+ T cell help, with active CTLs generated in BP-OVA vaccinated I-Ab-/- and CD40-/- mice. In contrast, IL-15 and type I IFN were required, with abrogated CTL activity in vaccinated IL-15-/- and IFNAR1-/- mice. cDC1 and/or CD103+ DCs were not essential for BP-OVA specific CTL with immunization eliciting responses in Batf3-/- mice. Poly I:C, but not LPS or CpG, co-administered as an adjuvant with BP-OVA boosted CTL responses. Finally, vaccination with BP-OVA protected against B16-OVA melanoma and Eµ-myc-GFP-OVA lymphoma inoculation. In summary, we have demonstrated that epitope-displaying BPs represent an antigen delivery platform exhibiting a unique mechanism to effectively engage T cell immune responses.

Targeting Tumor Heterogeneity with Neoantigen-Based Cancer Vaccines.

Neoantigen-based cancer vaccines have emerged as a promising immunotherapeutic approach to treat cancer. Nevertheless, the high degree of heterogeneity in tumors poses a significant hurdle for developing a vaccine that targets the therapeutically relevant neoantigens capable of effectively stimulating an immune response as each tumor contains numerous unique putative neoantigens. Understanding the complexities of tumor heterogeneity is crucial for the development of personalized neoantigen-based vaccines, which hold the potential to revolutionize cancer treatment and improve patient outcomes. In this review, we discuss recent advancements in the design of neoantigen-based cancer vaccines emphasizing the identification, validation, formulation, and targeting of neoantigens while addressing the challenges posed by tumor heterogeneity. The review highlights the application of cutting-edge approaches, such as single-cell sequencing and artificial intelligence to identify immunogenic neoantigens, while outlining current limitations and proposing future research directions to develop effective neoantigen-based vaccines.

Precision-engineering of subunit vaccine particles for prevention of infectious diseases.

Vaccines remain the best approach for the prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell vaccines but often show reduced immunogenicity. Subunit vaccines in particulate format show improved vaccine efficacy by inducing strong immune responses leading to protective immunity against the respective pathogens. Antigens with proper conformation and function are often required to induce functional immune responses. Production of such antigens requiring post-translational modifications and/or composed of multiple complex domains in bacterial hosts remains challenging. Here, we discuss strategies to overcome these limitations toward the development of particulate vaccines eliciting desired humoral and cellular immune responses. We also describe innovative concepts of assembling particulate vaccine candidates with complex antigens bearing multiple post-translational modifications. The approaches include non-covalent attachments (e.g. biotin-avidin affinity) and covalent attachments (e.g. SpyCatcher-SpyTag) to attach post-translationally modified antigens to particles.

Effect of ozone, lactic acid and combination treatments on the control of microbial and pesticide contaminants of fresh vegetables.

BACKGROUND: Fruit and vegetable consumption has increased due to their tremendous health benefits. However, recent studies have shown that contaminated products may serve as vehicles for foodborne pathogens and harmful chemicals. Therefore, fresh vegetables must be decontaminated before consumption to ensure food safety. RESULTS: In this study, the combined decontamination treatment of lactic acid (2.5 mL L-1 ) and ozone (9 mg L-1 ) for 10 min showed better efficacy in the removal of contaminants from fresh vegetables as compared to individual treatments. The combined treatment resulted in a reduction of 1.5-3.5 log CFU of native mesophilic bacteria per gram and 1.6-2.9 log CFU of artificially inoculated Escherichia coli per gram from tomato, cucumber, carrot and lettuce. The combined treatment also removed spiked pesticides, which represent artificial chemical contamination (28-97% chlorpyrifos and 62-100% λ-cyhalothrin residues), from fresh vegetables. No significant difference (P > 0.05) in various sensory attributes of vegetables was observed between untreated and treated (lactic acid and ozone) vegetables. CONCLUSIONS: The combination treatment provides a novel approach to target two groups of contaminants using a single procedure. The combination treatment can be used as an alternative to currently used decontamination techniques for the supply of safe vegetables to consumers. © 2020 Society of Chemical Industry.

Decontamination of Microorganisms and Pesticides from Fresh Fruits and Vegetables: A Comprehensive Review from Common Household Processes to Modern Techniques.

Fresh fruits and vegetables are a rich source of micronutrients. However, many foodborne illnesses have been linked to the consumption of fresh fruits and vegetables as they are reported to harbor contaminants such as microorganisms and pesticides. Recently reported foodborne outbreaks have been linked to a diverse group of fruits and vegetables due to the presence of various pathogens including Salmonella, Escherichia coli, and Listeria monocytogenes. Also, the increased use of pesticides has resulted in the deposition of chemical residues on the surface of fruits and vegetables, which has led to the adverse health conditions such as cancer, birth defects, and neurodevelopmental disorders. Fresh commodities are subjected to various treatments to prevent or minimize these outbreaks, and the main targets of such treatments have been the elimination of pathogens and degradation of toxic chemical residues. Here, we have discussed various decontamination methods including simple household washing, chemical treatments, and modern technologies with their mode of action for microbial and pesticide removal. The simple household processes are not very effective in the removal of pathogenic organisms and pesticides. The use of modern techniques like cold plasma, ozone, high hydrostatic pressure, and so on, showed better efficacy in the removal of microorganisms and pesticides. However, their industrial use is limited considering high installation and maintenance cost. In this review, we suggest combined methods based on their mode of decontamination and suitability for a selected fruit or vegetable for effective decontamination of microbes and pesticide together to reduce the treatment cost and enhance food safety.