Anti-dengue virus NS1 protein monoclonal antibodies
Inventors
Bosch, Irene • Hamad-Schifferli, Kimberly • Gomez-Marquez, Jose • Guixe, Helena dePuig • Gehrke, Lee
Assignees
Massachusetts Institute of Technology • US Department of Health and Human Services
Publication Number
US-11320433-B2
Publication Date
2022-05-03
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 novel monoclonal antibodies and matched antibody pairs for the specific detection of one or more of the four dengue virus serotypes in a biological sample. Each matched antibody pair is capable of detecting not more than one serotype of dengue virus NS1 protein present in the sample and does not cross react with other serotypes. These antibodies facilitate the development of confirmatory in vitro diagnostic tests such as sandwich immunoassays in a lateral flow format, which detect and distinguish the presence of dengue virus serotypes in biological samples, preferably human-derived samples.
Matched antibody pairs can be used individually to detect each serotype or combined for multiplex or pan-dengue detection on one or multiple assay strips. The antibodies are monoclonal and are specific to different epitopes on the NS1 protein of each dengue virus serotype, enabling sensitive and specific multiplexed detection. Kits comprising the matched antibody pairs and methods for using the kits are also provided. Moreover, the invention discloses the use of monoclonal antibodies specific to dengue NS1 protein as therapeutics for prevention and treatment of dengue virus infection.
The problem being solved is that dengue virus exists in four distinct serotypes which are antigenically distinct and cross-reactive serological tests do not provide cross-protective immunity or accurate serotype-specific diagnosis. Existing assays have limited sensitivity across all serotypes because of genetic diversity, and there is a need for an accurate diagnostic that can detect and distinguish all four dengue virus serotypes individually and with high specificity to inform clinical management and epidemiological surveillance.
Claims Coverage
The patent claims cover two independent inventive features focused on diagnostic kits comprising matched antibody pairs specific for dengue virus NS1 protein serotypes.
Matched antibody pairs specific for single dengue virus NS1 serotype
Diagnostic kits comprising at least one matched antibody pair selected from defined pairs of monoclonal antibodies, each pair specifically binding and detecting no more than one dengue virus NS1 protein serotype in a biological sample. Each antibody or fragment includes specified heavy chain and light chain variable regions and complementarity determining regions (CDRs) defined by SEQ ID NOs, enabling serotype-specific detection without cross-reactivity.
Diagnostic kits with matched antibody pairs exhibiting no cross-reactivity to Zika virus
Diagnostic kits as above wherein the matched antibody pairs do not detect any protein from Zika virus present in the biological sample, enhancing specificity for dengue virus detection.
The claims principally cover diagnostic kits comprising carefully selected matched monoclonal antibody pairs that detect individual dengue virus NS1 protein serotypes with high specificity and no cross-reactivity to closely related viruses such as Zika, including embodiments with detection labels and ELISA sandwich assay formats.
Stated Advantages
Enable detection and distinction of all four dengue virus serotypes in biological samples with high specificity.
Avoid cross-reactivity with other serotypes and related flaviviruses like Zika and yellow fever virus.
Facilitate development of confirmatory in vitro diagnostic tests suitable for point-of-care use, including lateral flow assays.
Allow multiplexed detection of multiple serotypes in a single assay strip for efficient diagnosis.
Provide monoclonal antibodies useful as therapeutic agents for prevention and treatment of dengue infection.
Assist in epidemiological surveillance and outbreak management by serotype-specific detection in patient populations.
Documented Applications
Use in confirmatory in vitro diagnostic tests such as sandwich immunoassays (e.g., lateral flow assays) to detect and distinguish each of the four dengue virus serotypes in biological samples.
Use in multiplexed or pan-dengue detection assays combining matched antibody pairs for simultaneous detection of multiple serotypes.
Inclusion in diagnostic kits comprising matched antibody pairs with or without detection labels, controls, buffers and related components for dengue virus testing.
Therapeutic use of monoclonal antibodies specific for dengue NS1 protein serotypes for prevention and treatment of dengue virus infections in humans.
Epidemiological surveillance and outbreak mapping of dengue virus serotypes in populations using the serotype-specific diagnostic assays.
Application in immunological assays such as ELISA, flow cytometry, and immunofluorescence to detect dengue NS1 protein in serum or infected cells.
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