Protection against human rhinovirus infection
Inventors
Blanco, Jorge C. G. • Kajon, Adriana E.
Assignees
SIGMOVIR BIOSYSTEMS Inc • Lovelace Respiratory Research Institute
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Publication Number
US-9121048-B1
Publication Date
2015-09-01
Expiration Date
Abstract
Methods, kits, and compositions are disclosed for vaccinating a human or animal against human rhinovirus infection. Also provided are methods of using a cotton rat model for identifying and testing vaccines and therapeutic agents that prevent or ameliorate human rhinovirus infection.
Core Innovation
The invention provides a method of identifying or testing a vaccine or therapeutic agent that reduces rhinovirus A (HRV-A) infection and/or reduces rhinovirus B (HRV-B) infection by assessing viral titers in lung tissue from cotton rats challenged intranasally with HRV-A and/or HRV-B. The approach compares a first test sample from cotton rats that receive a potential HRV-A and/or HRV-B vaccine or therapeutic agent with a second test sample from cotton rats that receive a control agent. A decrease in the titer of HRV-A and/or HRV-B in the first test sample as compared to the second test sample is indicative of reduced HRV-A infection and/or reduced HRV-B infection.
The disclosed work establishes a cotton rat (Sigmodon hispidus) challenge model for rhinovirus, where HRV16 intranasal infection yields measurable viral titers across nose, trachea, and lung and is associated with respiratory pathology. The model includes induction of interferon-stimulated genes such as Mx-1 and Mx-2, and it measures replication-related materials including genomic positive-strand RNA and replication intermediate negative-strand RNA. This provides readouts for comparing tissue viral titers in treated versus control groups.
The document further describes vaccination and therapeutic protection using live HRV, including antibody-mediated approaches such as passive transfer of immune serum and maternal transfer of immunity to offspring. Intramuscular vaccination with live HRV16 induces high serum neutralizing antibodies and reduces viral titers after intranasal challenge. Immune serum or antibodies transferred from vaccinated mothers protect offspring, supporting the use of the animal challenge/titer comparison approach for testing anti-rhinovirus vaccines and therapeutics.
Claims Coverage
The disclosed independent claim (clm-00001) covers a method for identifying or testing HRV-A and/or HRV-B vaccine or therapeutic agents using cotton rats and comparing lung viral titers after intranasal HRV challenge. The claim is supported by inventive feature refinements in dependent claims, including specific control agents, forms of the potential agent, and specified administration routes.
Cotton rat lung titer comparison for HRV-A/HRV-B reduction
Measuring the titer of HRV-A and/or HRV-B in lung derived from cotton rats challenged with HRV-A and/or HRV-B intranasally after administration of a potential HRV-A and/or HRV-B vaccine or therapeutic agent as a first test sample; measuring the titer of HRV-A and/or HRV-B in lung derived from cotton rats challenged with HRV-A and/or HRV-B intranasally after administration of a control agent as a second test sample; and determining whether there is a decrease in the titer of HRV-A and/or HRV-B in the first test sample as compared to the second test sample, wherein a decrease is indicative of identification of a vaccine or therapeutic agent that reduces HRV-A infection and/or reduces HRV-B infection.
Named control agent comparison
Selecting the control agent from saline, phosphate buffered saline (PBS), inert aqueous isotonic solutions, or ultraviolet (UV)-inactivated HRV-A or UV-inactivated HRV-B.
Potential agent as native protein or fragment
Using a potential HRV-A and/or HRV-B vaccine or therapeutic agent that is a native protein or a fragment of the native protein.
Potential agent as nucleic acid
Using a potential HRV-A and/or HRV-B vaccine or therapeutic agent in the form of a nucleic acid.
Potential agent administration route set
Administering the potential HRV-A and/or HRV-B vaccine or therapeutic agent using one of intramuscular, intradermal, intravenous, subcutaneous, or oral routes.
Across the independent claim and its dependents, the patent claim coverage centers on identifying or testing HRV-A/HRV-B vaccines or therapeutics by measuring lung HRV titers in cotton rats after intranasal challenge and comparing treated versus control groups, where a decrease indicates reduction of HRV infection. Dependent features further specify example control agents, specify representative forms of the potential agent (native protein/fragment or nucleic acid), and constrain the administration routes to a defined set.
Stated Advantages
A decrease in the titer of HRV-A and/or HRV-B in the treated (first test sample) compared to the control (second test sample) is indicative of identification of a vaccine or therapeutic agent that reduces HRV-A infection and/or reduces HRV-B infection.
Documented Applications
Testing anti-rhinovirus vaccines and therapeutics using the cotton rat challenge model by comparing tissue viral titers versus controls after HRV intranasal challenge.
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