Thu Aug 12 03:01:41 2021
(*212c3007*):: +public!
In further embodiments, the present invention provides a method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject an effective amount of a chimeric coronavirus spike protein, a nucleic acid molecule, a vector, a VRP, a VLP, a coronavirus particle, population and/or a composition of this invention, including any combination thereof, thereby treating a coronavirus infection in the subject.
Additionally provided herein is a method of preventing a disease or disorder caused by a coronavirus infection in a subject, comprising administering to the subject an effective amount of a chimeric coronavirus spike protein, a nucleic acid molecule, a vector, a VRP, a VLP, a coronavirus particle, population and/or a composition of this invention, including any combination thereof, thereby preventing a disease or disorder caused by a coronavirus infection in the subject.
Furthermore the present invention provides a method of protecting a subject from the effects of coronavirus infection, comprising administering to the subject an effective amount of a chimeric coronavirus spike protein, a nucleic acid molecule, a vector, a VRP, a VLP, a coronavirus particle, population and/or a composition of this invention, including any combination thereof, thereby protecting the subject from the effects of coronavirus infection.
The chimeric coronavirus spike proteins of this invention can be used to immunize a subject against infection by a newly emerging coronavirus, as well as treat a subject infected with a newly emerging coronavirus. For example, the chimeric subgroup 2b coronavirus spike proteins of this invention can be used to immunize against and/or treat infection by bat SARS CoV like virus strains such as Rs SHC014 (GenBank® Accession No. KC881005), Rs3367 (GenBank® Accession No. KC881006) and/or WiV1 S (GenBank® Accession No. KC881007).
In yet further embodiments, the present invention provides a method of identifying a coronavirus spike protein for administration to elicit an immune response to coronavirus in a subject infected by a coronavirus and/or a subject at risk of coronavirus infection and/or to a subject for whom eliciting an immune response to a coronavirus is needed or desired, comprising: a) contacting a sample obtained from a subject infected with a coronavirus with a panel of proteins comprising: 1) one or more chimeric coronavirus spike proteins from a subgroup 2c coronavirus, 2) one or more chimeric coronavirus spike proteins from a subgroup 2b coronavirus, 3) one or more spike proteins from a subgroup 2a coronavirus, 4) one or more chimeric coronavirus spike proteins from a subgroup 2d coronavirus, 5) one or more chimeric coronavirus spike proteins from a subgroup 1a coronavirus, 6) one or more chimeric coronavirus spike proteins from a subgroup 1b coronavirus, 7) one or more chimeric coronavirus spike proteins from a subgroup 3 coronavirus and 8) any combination of (1) through (7) above, under conditions whereby an antigen/antibody complex can form; and b) detecting formation of an antigen/antibody complex, whereby detection of formation of the antigen/antibody complex comprising the chimeric coronavirus spike protein(s) of any of (1)-(6) identifies the presence of antibodies to a spike protein of the coronavirus that is infecting the subject of (a), thereby identifying a coronavirus spike protein for administration to the subject of (a) and/or to a subject infected with a coronavirus and/or to a subject at risk of coronavirus infection and/or to a subject for whom eliciting an immune response to a coronavirus is needed or desired.
(*212c3007*):: In some embodiments, the method set forth above can further comprise the step of administering the coronavirus spike protein identified according to the method to the subject of (a) and/or to a subject at risk of coronavirus infection and/or to a subject infected with a coronavirus and/or to a subject for whom eliciting an immune response to a coronavirus is needed or desired.
A method is also provided herein of identifying an antibody that neutralizes a coronavirus infecting a subject, comprising: a) isolating a coronavirus from a sample of a subject infected with a coronavirus and/or suspected of being infected with a coronavirus; b) contacting the coronavirus of (a) with a panel of antibodies comprising: 1) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 2c coronavirus, 2) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 2b coronavirus, 3) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 2a coronavirus, 4) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 2d coronavirus, 5) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 1a coronavirus, 6) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 1b coronavirus, 7) an antibody reactive with a chimeric coronavirus spike protein from a subgroup 3 coronavirus, and 8) any combination of (1) through (7) above, to form respective coronavirus/antibody compositions, each comprising a respective antibody of the panel; c) contacting each of the respective coronavirus/antibody compositions of (b) with cells susceptible to coronavirus infection under conditions whereby coronavirus infection can occur; and d) detecting the presence or absence of infection of the cells, whereby absence of detection of infection of the cells contacted with any of the coronavirus/antibody compositions of (b) identifies the antibody of that coronavirus/antibody composition as an antibody that neutralizes the coronavirus infecting the subject.
In some embodiments, the method set fort above can further comprise the step of administering the antibody identified according to the method to the subject of (a) and/or to a subject infected with a coronavirus and/or to a subject at risk of coronavirus infection and/or to a subject for whom eliciting an immune response to a coronavirus is needed or desired.
As used herein, “a” or “an” or “the” can mean one or more than one. For example, “a” cell can mean one cell or a plurality of cells.
Also as used herein, “and/or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).
Furthermore, the term “about,” as used herein when referring to a measurable value such as an amount of a compound or agent of this invention, dose, time, temperature, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1% of the specified amount.
As used herein, the transitional phrase “consisting essentially of” means that the scope of a claim is to be interpreted to encompass the specified materials or steps recited in the claim, “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention. See, In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976) (emphasis in the original); see also MPEP §2111.03.
A “sample” or “biological sample” of this invention can be any biological material, such as a biological fluid, an extract from a cell, an extracellular matrix isolated from a cell, a cell (in solution or bound to a solid support), a tissue, a tissue homogenate, and the like as are well known in the art.
(*212c3007*):: In the methods of this invention in which formation of an antigen/antibody complex is detected, a variety of assays can be employed for such detection. For example, various immunoassays can be used to detect antibodies or proteins (antigens) of this invention. Such immunoassays typically involve the measurement of antigen/antibody complex formation between a protein or peptide (i.e., an antigen) and its specific antibody.
The immunoassays of the invention can be either competitive or noncompetitive and both types of assays are well-known and well-developed in the art. In competitive binding assays, antigen or antibody competes with a detectably labeled antigen or antibody for specific binding to a capture site bound to a solid surface. The concentration of labeled antigen or antibody bound to the capture agent is inversely proportional to the amount of free antigen or antibody present in the sample.
Noncompetitive assays of this invention can be, for example, sandwich assays, in which, for example, the antigen is bound between two antibodies. One of the antibodies is used as a capture agent and is bound to a solid surface. The other antibody is labeled and is used to measure or detect the resultant antigen/antibody complex by e.g., visual or instrument means. A number of combinations of antibody and labeled antibody can be used, as are well known in the art. In some embodiments, the antigen/antibody complex can be detected by other proteins capable of specifically binding human immunoglobulin constant regions, such as protein A, protein L or protein G. These proteins are normal constituents of the cell walls of streptococcal bacteria. They exhibit a strong nonimmunogenic reactivity with immunoglobulin constant regions from a variety of species. (See, e.g., Kronval et al. J. Immunol. 111:1401-1406 (1973); Akerstrom et al. J. Immunol. 135:2589-2542 (1985)).
In some embodiments, the non-competitive assays need not be sandwich assays. For instance, the antibodies or antigens in the sample can be bound directly to the solid surface. The presence of antibodies or antigens in the sample can then be detected using labeled antigen or antibody, respectively.