The present disclosure relates, generally, to compositions and methods for producing, purifying, and using circular RNA.

The disclosure provides an animal cell stably expressing a virus-like particle (VLP). The disclosure also provides a method for manufacturing a virus-like particle, a virus-like particle, a vaccine composition, a method for preventing viral infection, and a method for producing antibodies.

Systems and methods for culture of human kidney organoids as a model system for characterizing kidney pathologies and implementing therapeutics for conditions that affect the kidney. A model system for characterization of a pathophysiology includes a culture of human kidney organoids and an organoid culture medium. The organoids may include one or more genome edits as part of an approach for studying genetic factors involved with a pathological process. The culture may include one or more other factors, such as pathological agents and/or anti-pathological agents, for development and evaluation of therapeutics. The approaches may be used for implementation of compositions and methods for virally transducing the kidney or a subset of cells or cell types thereof.

A protein, such as an antigenic protein, is produced by determining an amino acid sequence of an ancestral version of a given protein in an ancestral sequence reconstruction method based on a plurality of homologous amino acid sequences of the given protein. A domain of the amino acid sequence of the ancestral version of the given protein is replaced with a corresponding domain derived from an amino acid sequence of the given protein or a homologous version thereof. The protein thereby comprises the amino acid sequence obtained by replacing the domain of the amino acid sequence of the ancestral version of the given protein with the corresponding domain derived from the amino acid sequence of the given protein or the homologous version thereof. The protein is suitable as antigen, as vaccine candidate and/or for structural studies.

The present disclosure relates to modified coronavirus S protein and virus-like particles (VLPs) comprising modified coronavirus S protein. The present invention also relates to methods of increasing the purity, and/or stability of coronavirus S protein or VLPs comprising modified coronavirus S protein in a host or host cell.

Engineered SARS-CoV-2 variants having a combination of attenuating modifications, and their use as live-attenuated SARS-CoV-2 vaccines, are described. The recombinant genome of the live-attenuated SARS-CoV-2 encodes a modified spike (S) protein with a deletion of the polybasic site (PRRA); encodes a modified non-structural protein 1 (Nsp1) with K164A and H165A substitutions; and includes a mutation that prevents expression of open reading frames (ORFs) 6, 7a, 7b and 8. The disclosed live-attenuated SARS-CoV-2 retain the capacity to infect and replicate in mammalian cells. Immunogenic compositions that include a live-attenuated SARS-CoV-2 and methods of eliciting an immune response against SARS-CoV-2 in a subject are also described. Further disclosed are a collection of reverse genetics plasmids that include the complement of the recombinant genome of the live-attenuated SARS-CoV-2 and methods of producing a live-attenuated SARS-CoV-2 using the reverse genetics plasmids.

This invention relates to adjuvant formulations comprising various combinations of triterpenoids, sterols, immunomodulators, polymers, and Th2 stimulators; methods for making the adjuvant compositions; and the use of the adjuvant formulations in immunogenic and vaccine compositions with different antigens. This invention further relates to the use of the formulations in the treatment of animals.

The invention provides competitive particles, such as virus-like particles, RNAs and DNAs for the treatment or prevention of viral infections and methods of using such particles for treating or preventing or reducing the risk of viral infections (or symptoms thereof) in a subject, such as a human or animal subject. For example, the method herein is a method of reducing or reducing the establishment of a zoonotic population of a virus in an animal, such as a livestock or wild animal (eg, a bat, camelid or a Pholidota (eg, a pangolin)).

The present invention relates to a production method of an inactivated SARS-CoV-2 vaccine, the method including: a step of bringing a SARS-CoV-2 containing solution or an inactivated SARS-CoV-2 containing solution into contact with a cellulose sulfate ester gel at a pH of 8 or more and 10 or less to adsorb the SARS-CoV-2 or the inactivated SARS-CoV-2 to the gel; then removing impurities; and then eluting and recovering the SARS-CoV-2 or the inactivated SARS-CoV-2.

A MERS-CoV vaccine with nucleic acid sequences having at least 90% identity to the spike gene of a MERS-CoV strain as a preventive measure against MERS-CoV infections is described. The nucleic acid sequences may include plasmid DNA (pDNA) or messenger RNA (mRNA) that are encapsulated by aluminosilicates. The aluminosilicates may be functionalized with aminopropyltrimethoxysilanes.