Anti-dengue virus NS1 protein monoclonal antibodies
Inventors
Bosch, Irene • Hamad-Schifferli, Kimberly • Gomez-Marquez, Jose • de Puig, Helena • Gehrke, Lee
Assignees
Food And Drug Administration • Massachusetts Institute of Technology • US Department of Health and Human Services
Publication Number
US-10551381-B2
Publication Date
2020-02-04
Expiration Date
2037-02-10
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Abstract
The present invention provides matched antibody pairs for the specific detection of one or more of the four dengue virus serotypes in a biological sample that may contain one or more of such dengue virus serotypes. Each matched antibody pair is capable of detecting not more than one serotype of dengue virus NS1 protein that may be present in the sample and will not cross react with other serotypes that may be present in the sample. Multiple matched pairs may be used to detect one or more dengue virus serotypes that may be present in a sample. Such matched pair antibodies, facilitate the development of confirmatory in vitro diagnostic tests such as sandwich immunoassays, that detect and distinguish the presence of one or more dengue virus serotypes in a biological sample, preferably a sample derived from human subject. The invention also provides kits comprising the matched antibody pairs of the invention and methods for using the kits for immunoassays for the specific detection of one or more serotypes of dengue virus in a patient population. The present invention also provides monoclonal antibodies specific for the NS1 protein of dengue virus and therapeutic compositions and methods for treating dengue virus infection.
Core Innovation
The invention provides matched antibody pairs specifically designed for the detection of one or more of the four dengue virus serotypes in biological samples that may contain these serotypes. Each matched antibody pair is capable of specifically detecting no more than one dengue virus NS1 protein serotype and does not cross-react with other serotypes present in the sample. This specificity facilitates the development of confirmatory in vitro diagnostic tests, such as sandwich immunoassays, that can both detect and distinguish between dengue virus serotypes, preferably using biological samples derived from human subjects.
The matched antibody pairs can be used individually or in combination to detect one or more dengue virus serotypes in a sample, allowing for Pan detection or serotype-specific detection in various assay configurations including lateral flow assays and dipstick formats. The invention also includes kits comprising these matched antibody pairs and methods for their use in immunoassays for specific dengue virus serotype detection. Moreover, the invention provides monoclonal antibodies specific for the NS1 protein of dengue virus serotypes and therapeutic compositions and methods for treating dengue virus infection.
The problem addressed by the invention is the need for an accurate diagnostic capable of detecting and distinguishing all four dengue virus serotypes despite the limited relatedness of the viral targets at the nucleic acid level. Prior attempts at a single assay with high sensitivity for all serotypes have been hampered by extensive cross-reactivity in serological tests and lack of cross-protective immunity, making precise serotype identification critical for diagnosis and treatment. Existing limitations include difficulties in serotype-specific detection due to antigenic similarity within the flavivirus family and cross-reactivity issues, which the invention overcomes through the use of highly specific matched antibody pairs.
Claims Coverage
The patent claims five main inventive features defined by matched antibody pairs for dengue virus NS1 serotype-specific detection in a diagnostic kit.
Diagnostic kit comprising matched antibody pairs specific for dengue NS1 serotypes
A diagnostic kit including at least one matched antibody pair that specifically binds and detects no more than one dengue virus NS1 protein serotype in a biological sample. The matched pairs are selected from five distinct combinations of monoclonal antibodies or antigen binding fragments with specified heavy and light chain variable region CDR sequences (SEQ ID NOs), enabling serotype-specific detection.
Specificity excluding detection of Zika virus proteins
The matched antibody pairs in the diagnostic kit do not detect any Zika virus protein present in the biological sample, ensuring assay specificity within flavivirus family viruses.
Incorporation of detection labels on at least one antibody
At least one antibody of each matched antibody pair in the diagnostic kit is conjugated with a detection label to facilitate signal detection in immunoassays.
Varied types of detection labels compatible with the antibody pairs
The detection labels used on antibodies include biotin, avidin, gold nanoparticles, colored latex beads, magnetic particles, carbon nanoparticles, selenium nanoparticles, silver nanoparticles, quantum dots, up converting phosphors, organic fluorophores, textile dyes, enzymes, and liposomes, accommodating multiple assay formats.
Exclusion of detection of yellow fever virus proteins
The matched antibody pairs in the diagnostic kit do not detect yellow fever virus proteins in samples, improving specificity for dengue virus NS1 protein serotypes.
The claims focus on the composition of diagnostic kits incorporating specific matched antibody pairs that enable serotype-specific detection of dengue virus NS1 proteins while excluding cross-reactivity with related viruses such as Zika and yellow fever. Features include antibody variable region CDR sequences, conjugation with detectable labels, and compatibility with various detection modalities.
Stated Advantages
Enables specific detection and distinction among the four dengue virus serotypes in biological samples, enhancing diagnostic accuracy.
Facilitates confirmatory in vitro diagnostic tests such as sandwich immunoassays and lateral flow assays that are sensitive and specific.
Allows for multiplexed detection in single or multiple assay strips, including pan-dengue detection and serotype-specific mapping.
Reduces cross-reactivity with related flaviviruses, such as Zika and yellow fever viruses, improving diagnostic specificity.
Supports point-of-care diagnostics through lateral flow assay formats that are robust, inexpensive, and do not require specialized equipment or cold chain storage.
Provides monoclonal antibodies useful not only for diagnostics but also as therapeutic agents for the prevention and treatment of dengue virus infection.
Documented Applications
Diagnosis of dengue virus infection by detecting and distinguishing dengue virus NS1 protein serotypes in biological samples, including human serum.
Development of confirmatory in vitro diagnostic tests, particularly sandwich immunoassays and lateral flow assays for point-of-care testing.
Use in kits comprising matched antibody pairs for specific detection of dengue virus serotypes in patient populations.
Therapeutic applications involving treatment and prevention of dengue virus infections using monoclonal antibodies targeting NS1 proteins.
Epidemiological surveillance and public health monitoring to map serotype prevalence and assess risk of dengue hemorrhagic fever outbreaks.
Application in flow cytometry and immunofluorescence assays to detect dengue virus-infected cells in vitro or in vivo.
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