The present invention provides a live, attenuated coronavirus comprising a variant replicase gene encoding polyproteins comprising a mutation in one or more of non-structural protein(s) (nsp)-10, nsp-14, nsp-15 or nsp-16. The coronavirus may be used as a vaccine for treating and/or preventing a disease, such as infectious bronchitis, in a subject.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

The present invention relates i.a. to an IBV (infectious bronchitis virus) deposited with the BVR of IZSLER under accession number DPS RE RSCIC 16, any descendant IBV thereof and any IBV having all of the identifying characteristics of the deposited IBV. Further, the present invention relates to an immunogenic composition comprising said deposited IBV.

Described herein is an immortalized mammalian cell configured for production of a bioproduct of interest, which cell has a safe harbor locus selected from an Adeno Associated Virus 1 (AAVS1) locus, a CCR5 locus, and a Rosa26 locus into which a Human Papillomavirus (HPV) E6 gene sequence and an HPV E7 gene sequence have been inserted. Also disclosed herein are methods for immortalizing a mammalian cell for production of a bioproduct of interest as well as methods of producing a bioproduct of interest.

The invention relates to a polynucleotide encoding an attenuated SARS-CoV-2 or a fragment thereof, wherein the polynucleotide comprises at least 20 one-to-stop codons. The polynucleotide may comprise further modifications and may be comprised in an attenuated SARS-CoV-2. The invention further relates to methods for production of the polynucleotide and pharmaceutical products, e.g. for medical use.

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.

Attenuate coronavirus species that are able to fully replicate and spread are proposed together with the methods of obtaining thereof. The proposed coronavirus species are intended to treat and prevent viral infections including all those caused by coronavirus species that affect humans as the COVID-19 caused by the SARS-CoV2. Compared with other treatment or vaccine alternatives, the availability of such attenuate coronavirus species does not require of significant distribution and production resources. Some of the embodiments of the invention involve the use of the attenuate coronavirus species in formulations or compositions that have to be approved as safe and effective for therapeutic use in specific territories by a valid regulatory agency as the Food and Drug Agency (FDA) in the United States.

Attenuate coronavirus species that are able to fully replicate and spread are proposed together with the methods of obtaining thereof. The proposed coronavirus species are intended to treat and prevent viral infections including all those caused by coronavirus species that affect humans as the COVID-19 caused by the SARS-CoV2. Compared with other treatment or vaccine alternatives, the availability of such attenuate coronavirus species does not require of significant distribution and production resources. Some of the embodiments of the invention involve the use of the attenuate coronavirus species in formulations or compositions that have to be approved as safe and effective for therapeutic use in specific territories by a valid regulatory agency as the Food and Drug Agency (FDA) in the United States.

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)).