High-Content Screening and Computational Prediction Reveal Viral Genes That Suppress the Innate Immune Response.

Suppression of the host innate immune response is a critical aspect of viral replication. Upon infection, viruses may introduce one or more proteins that inhibit key immune pathways, such as the type I interferon pathway. However, the ability to predict and evaluate viral protein bioactivity on targeted pathways remains challenging and is typically done on a single-virus or -gene basis.

Theranostic cells: emerging clinical applications of synthetic biology.

Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering include the development of cells that function in biological samples or within the body as minimally invasive diagnostics or theranostics for the real-time regulation of complex diseased states. Ex vivo and in vivo cell-based biosensors and therapeutics have been developed to target a wide range of diseases including cancer, microbiome dysbiosis and autoimmune and metabolic diseases.

Protein and Peptide Nanocluster Vaccines.

Recombinant protein- and peptide-based vaccines can deliver large amounts of specific antigens for tailored immune responses. One class of these are protein and peptide nanoclusters (PNCs), which are made entirely from the crosslinked antigen. PNCs leverage the inherent immunogenicity of nanoparticulate antigens while minimizing the use of excipients normally used to create them.

Beyond the Four Bases: A Home Run for Synthetic Epigenetic Control?

Park et al. (2019) create a synthetic self-propagating adenine methylation system for epigenetic control in human cells. Targeting adenine allows their modular system to act orthogonally to most epigenetic processes, thereby opening the door for novel methods of controlling gene expression.

H7 Hemagglutinin nanoparticles retain immunogenicity after >3 months of 25°C storage.

Vaccine distribution infrastructure remains inadequate in many parts of the world, and it is estimated that up to 40-50% of all vaccine doses are wasted in certain countries. Vaccines that can maintain viability outside of the cold chain would decrease vaccine wastage and increase immunization rates in regions of the world with underdeveloped vaccine distribution infrastructure. We examined the potential of crosslinked protein nanoparticles, made from trimerized influenza hemagglutinin (3HA), to maintain immunogenicity after cold-chain-independent storage.

Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice.

Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating.

Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.

Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine.

Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge.

Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses.

Host- and pathogen-derived adjuvant coatings on protein nanoparticle vaccines.

Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from and mice, respectively, are representatives of pathogen- and host-derived molecules that can enhance immune responses.

Effects of ovalbumin protein nanoparticle vaccine size and coating on dendritic cell processing.

Nanoparticle vaccine delivery platforms are a promising technology for enhancing vaccine immunogenicity. Protein nanoparticles (PNPs), made entirely from antigen, have been shown to induce protective immune responses against influenza. However, the fundamental mechanisms by which PNPs enhance component protein immunogenicity are not understood.

Coated protein nanoclusters from influenza H7N9 HA are highly immunogenic and induce robust protective immunity.

Recurring influenza viruses pose an annual threat to public health. A time-saving, cost-effective and egg-independent influenza vaccine approach is important particularly when responding to an emerging pandemic. We fabricated coated, two-layer protein nanoclusters from recombinant trimeric hemagglutinin from an avian-origin H7N9 influenza A virus as an approach for vaccine development in response to an emerging pandemic.

Nanoclusters self-assembled from conformation-stabilized influenza M2e as broadly cross-protective influenza vaccines.

Unlabelled: Influenza vaccines with broad cross-protection are urgently needed. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) can be a promising candidate if its low immunogenicity was overcome. In this study, we generated protein nanoclusters self-assembled from conformation-stabilized M2e tetramers (tM2e) to improve its immunogenicity.