C12N2760/18562

LIVE ATTENUATED VACCINES FOR PNEUMOVIRUSES AND RELATED METHODS AND MATERIALS
20180066238 · 2018-03-08 ·

Described herein are mutant pneumoviruses comprising a nucleotide sequence which encodes a mutated zinc binding motif in an M2-1 protein of the pneumovirus, wherein the zinc binding motif is mutated relative to wild-type pneumovirus. The mutant pneumoviruses described herein grow to high titer in cell culture, are genetically stable, are attenuated in vitro and in vivo, and are highly immunogenic. Also described herein are vaccines and vaccine compositions comprising the live attenuated mutant pneumoviruses. Vaccine compositions can further comprise a pharmaceutically acceptable carrier, vehicle, excipient, and/or adjuvant. Methods for inducing a protective immune response in a subject against a pneumovirus infection are also described and disclosed. The vaccine compositions and methods described herein can be used to prevent metapneumovirus and respiratory syncytial virus infection in humans, respiratory syncytial virus infection in cattle, avian metapneumovirus infection in various avian species, and pneumonia virus of mice in rodents.

Respiratory syncytial virus with a genomic deficiency complemented in trans

The invention relates to pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.

ATTENUATION OF HUMAN RESPIRATORY SYNCYTIAL VIRUS BY GENOME SCALE CODON-PAIR DEOPTIMIZATION

Described herein are RSV polynucleotide sequences that make use of multiple codons that are containing silent nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce a numerous synonymous codons into the genome. Due to the large number of defects involved, the attenuated viruses disclosed herein provide a means of producing attenuated, live vaccines against RSV.

Recombinant RSV with silent mutations, vaccines, and methods related thereto

In certain embodiments, the disclosure relates to the polynucleotide sequences of respiratory syncytial virus (RSV). In certain embodiments, the disclosure relates to isolated or recombinant nucleic acids and polypeptides comprising desirable nucleic acid sequences and mutations disclosed herein. In certain embodiments, isolated or recombinant RSV comprising the nucleic acids and polypeptides disclosed herein (e.g., attenuated recombinant RSV) are also provided, as are immunogenic compositions including such nucleic acids, polypeptides, and RSV genomes that are suitable for use as vaccines. Attenuated or killed RSV containing these nucleic acids and mutation in the form of copied nucleic acids (e.g., cDNAs) are also contemplated.

Modified RSV F proteins and methods of their use

The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.

Modified RSV F proteins and methods of their use

The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.

GENETICALLY STABLE LIVE ATTENUATED RESPIRATORY SYNCYTIAL VIRUS VACCINE AND ITS PRODUCTION

Provided herein are recombinant respiratory syncytial viruses that contain mutations that make the disclosed viruses attractive vaccine candidates. The viruses disclosed contain attenuating mutations designed to have increased genetic and phenotypic stability. Desired combinations of these mutations can be made to achieve desired levels of attenation. Exemplary vaccine candidates are described. Also provided are polynucleotides capable of encoding the described viruses, as wells as methods for producing the viruses and methods of use.

Modified RSV F proteins and methods of their use

The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.

Methods and compositions for treating negative-sense single-stranded RNA virus

The current disclosure relates to methods, compositions and kits for detecting modified adenosine in a target RNA molecule. Aspects relate to a method for detecting modified adenosine in a target ribonucleic acid (RNA) comprising contacting the target RNA with an adenosine deaminase enzyme (adenosine deaminase, RNA-specific) to generate a target RNA with deaminated adenosines and sequencing the target RNA with deaminated adenosines; wherein the modified adenosine is detected when the nucleotide sequence includes adenosine within a m6A motif.

Genetically stable live attenuated respiratory syncytial virus vaccine and its production

Provided herein are recombinant respiratory syncytial viruses that contain mutations that make the disclosed viruses attractive vaccine candidates. The viruses disclosed contain attenuating mutations designed to have increased genetic and phenotypic stability. Desired combinations of these mutations can be made to achieve desired levels of attenation. Exemplary vaccine candidates are described. Also provided are polynucleotides capable of encoding the described viruses, as wells as methods for producing the viruses and methods of use.