Chimeric vectors
Inventors
Munir, Shirin • Brock, Linda G. • Buchholz, Ursula J. • Collins, Peter L.
Assignees
US Department of Health and Human Services
Publication Number
US-12071632-B2
Publication Date
2024-08-27
Expiration Date
2039-04-23
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Abstract
Disclosed are live, chimeric non-human Mononegavirales vectors that allow a cell to express at least one protein from at least one human pathogen. In addition, compositions comprising the vectors, methods and kits for eliciting an immune response in a host, and methods of making the vectors are disclosed, in accordance with embodiments of the invention.
Core Innovation
The invention provides live, chimeric non-human Mononegavirales vectors that allow a cell to express at least one protein from at least one human pathogen. These vectors are compositions that can be used to elicit an immune response in a host, and methods and kits for making and using such vectors are disclosed.
The invention addresses the problem of the need for improved ways to prevent and treat infections caused by human pathogens, particularly viruses such as the human respiratory syncytial virus (RSV). Existing vectors often face limitations such as instability of inserted sequences during replication, potential safety issues, and restrictions due to prior immunity in humans.
Unexpectedly, the murine pneumonia virus (MPV) genome is identified as an ideal vector for delivering heterologous antigens from human pathogens because it is small, easily manipulated, and allows stable insertion of non-native genes that remain stable during replication both in vitro and in vivo. MPV is attenuated in humans due to host range restriction, replicates in superficial epithelial cells of the respiratory mucosa without being highly invasive, does not integrate into or perturb the host genome, has low incidence of recombination, and does not face immunity restrictions from related viruses such as RSV.
Furthermore, MPV induces both local mucosal and systemic immune responses when replicating in the respiratory tract, making it particularly suitable as a safe and effective vector for respiratory pathogens. The invention illustrates methods for construction, administration, and composition formulation of such live, chimeric vectors that express proteins from human pathogens, exemplified by RSV F protein.
Claims Coverage
The patent includes several claims with multiple inventive features centered around a live chimeric murine pneumonia virus vector and compositions and methods related to it.
Live chimeric MPV vector expressing proteins from human viruses
A live, chimeric murine pneumonia virus (MPV) vector that allows a cell to express at least one protein from at least one human pathogen, wherein the pathogen is a virus.
Human Pneumoviridae virus as the pathogen source
The vector expresses at least one protein from a human Pneumoviridae virus.
Expression of RSV F and G proteins
The vector expresses RSV F protein and/or RSV G protein from human respiratory syncytial virus (RSV).
Sequences with high identity to specified SEQ ID NOs
The MPV vector comprises sequences with at least 90% identity to SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62.
Composition comprising the MPV vector and pharmaceutically acceptable carrier
A composition includes the MPV vector and a pharmaceutically acceptable carrier formulated for administration, optionally intranasal.
Methods of making live chimeric MPV vector
Methods comprising inserting a non-native gene encoding at least one protein from at least one human pathogen virus into an MPV vector.
Kit for eliciting immune response
A kit includes the composition containing the MPV vector and at least one container for holding the composition.
Method for eliciting immune response by administering MPV vector
Method of eliciting an immune response to at least one human pathogen by administering the MPV vector to a human.
MPV vector producing RSV F protein with at least 85% amino acid identity
The MPV vector allows cells to produce RSV F protein comprising an amino acid sequence with at least 85% identity to specific SEQ ID NOs: 57 or 59.
Expression of Spike protein from human Coronaviridae viruses
The MPV vector allows expression of a Spike protein from human Coronaviridae viruses including SARS and MERS coronaviruses.
The claims cover a live chimeric MPV vector expressing proteins from human viral pathogens especially Pneumoviridae and Coronaviridae, compositions comprising such vectors, methods of making and using the vectors to elicit immune responses, and kits for administration, emphasizing expression of RSV F protein and sequences closely matching specified SEQ ID NOs.
Stated Advantages
The MPV genome is relatively small and easily manipulated by reverse genetics to introduce heterologous genes.
Inserted non-native sequences in MPV are unusually stable during replication in vitro and in vivo, unlike many other vectors.
MPV is safe as it replicates in superficial respiratory epithelial cells without systemic invasion and does not integrate into the host genome.
Due to host range restriction, MPV is attenuated in humans and non-human primates, making it a stable and safe vector.
There is no pre-existing immunity against MPV in humans, avoiding neutralization or restriction by existing immunity against related viruses like RSV.
MPV induces both local mucosal immunity in the respiratory tract and systemic immunity, improving protection against respiratory pathogens.
Documented Applications
Compositions comprising live, chimeric non-human Mononegavirales vectors for administration to humans to elicit immune responses against human pathogens.
Methods of eliciting an immune response to human pathogens by administering such vectors or compositions to humans, including prophylactic immunization.
Use of MPV vectors expressing RSV F protein to induce immunity in RSV-naïve or RSV-experienced populations.
Formulation of vectors and compositions for various administration routes including intranasal, intramuscular, subcutaneous, and mucosal.
Kits containing the vector compositions and containers with instructions and administering components for vaccination.
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