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Must read!!!! https://patentimages.storage.googleapis.com/e9/b6/97/dc46ea622f9331/WO2021155323A1.pdf"Compositions and methods for preventing and treating coronavirus infection-sars-cov-2 vaccinesAbstractThe invention relates to immunogenic compositions and vaccines containing a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; also referred to as SARS-CoV-2)) protein or a polynucleotide encoding a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) protein and uses thereof. The invention also provides methods of treating and/or preventing a coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) infection by administering an immunogenic composition or vaccine to a subject (e.g., a human). The invention also provides methods of detecting and/or monitoring a protective anti-coronavirus (e.g., Wuhan coronavirus (2019-nCoV; SARS-CoV-2)) antibody response (e.g., anti-coronavirus antibody response, e.g., anti-2019- nCoV antibody response, e.g., anti-Spike antibody response, e.g., anti-Spike neutralizing antibody response). The present invention relates to isolated nucleic and/or recombinant nucleic acid encoding a coronavirus S protein, in particular a SARS-CoV-2 S protein, and to the coronavirus S proteins, as well as to the use of the nucleic acids and/or proteins thereof in vaccines.Classifications A61P31/14 Antivirals for RNA virusesView 18 more classificationsWO2021155323A1WIPO (PCT) Download PDF Find Prior Art SimilarOther languagesFrenchInventorDan H. BarouchJohannes Petrus Maria LANGEDIJKLucy RUTTENMark Johannes Gerandus BAKKERSRinke BosFrank WegmannDavid Adrianus Theodorus Maria ZUIJDGEESTAn VandeboschMathieu Claude Michel LE GARSJerald C. SadoffWorldwide applications2021 WO US UY USApplication PCT/US2021/015946 events 2020-01-31Priority to US202062969008P2021-01-30Application filed by Beth Israel Deaconess Medical Center, Inc., Janssen Pharmaceuticals, Inc.2021-08-05Publication of WO2021155323A1Show all eventsInfoPatent citations (6) Non-patent citations (3) Cited by (1) Legal events Similar documents Priority and Related ApplicationsExternal linksEspacenetGlobal DossierPatentScopeDiscussDescriptionCOMPOSITIONS AND METHODS FOR PREVENTING AND TREATING CORONAVIRUSINFECTION - SARS-COV-2 VACCINESINTRODUCTIONThe invention relates to the fields of virology and medicine. In particular, the invention relates to vaccines for the prevention of disease induced by SARS-CoV-2.CROSS REFERENCE TO RELATED APPLICATIONSThis application claims priority to U.S. Provisional Application No. 62/969,008, filed January 31, 2020; U.S. Provisional Application No. 62/994,630, filed March 25, 2020; U.S. Provisional Application No. 63/014,467, filed April 23, 2020; U.S. Provisional Application No. 63/025,782, filed May 15, 2020; U.S. Provisional Application No. 62/705,187, filed June 15, 2020; U.S. Provisional Application No. 62/705,308, filed June 21, 2020; U.S. Provisional Application No. 63/043,090, filed June 23, 2020; U.S Provisional Application No. 62/706,366, filed August 12, 2020; U.S. Provisional Application No. 63/066,147, filed August 14, 2020; U.S. Provisional Application No. 62/706,676, filed September 2, 2020; U.S. Provisional Application No. 62/706,937, filed September 18, 2020; U.S. Provisional Application No. 62/706,958, filed September 21, 2020; U.S. Provisional Application No. 63/198,089, filed September 28, 2020; U.S. Provisional Application No. 63/198,306, filed October 9, 2020; U.S. Provisional Application No. 63/112,900, filed on November 12, 2020; Canadian Patent Application No. 3,101,131, filed November 28, 2020; U.S. Provisional Application No. 63/121,482, filed December 4, 2020; U.S. Provisional Application No. 63/133,969, filed January 5, 2021; U.S. Provisional Application No. 63/135,182, filed January 8, 2021; U.S. Provisional Application No. 63/141,913, filed January 26, 2021; U.S. Provisional Application No. 63/142,977, filed January 28, 2021. Each disclosure is incorporated by reference in its entirety.SEQUENCE LISTINGThe instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy, created on January 29, 2021, is named CRU6043WOPCT and is 1.36 MB in size.STATEMENT AS TO FEDERALLY FUNDED RESEARCHThis invention was made with Government support under Agreement HHS0100201700018C, awarded by HHS. The Government has certain rights in the invention. BACKGROUNDSARS-CoV-2 is a coronavirus that was first discovered late 2019 in the Wuhan region in China. SARS-CoV-2 is a beta-coronavirus, like MERS-CoV and SARS-CoV, all of which have their origin in bats. There are currently several sequences available from several patients from the U.S., China and other countries, suggesting a likely single, recent emergence of this virus from an animal reservoir. The name of this disease caused by the virus is coronavirus disease 2019, abbreviated as COVID-19. Symptoms of COVID-19 range from mild symptoms to severe illness and death for confirmed COVID-19 cases.As indicated above, SARS-CoV-2 has strong genetic similarity to bat coronaviruses, from which it likely originated, although an intermediate reservoir host such as a pangolin is thought to be involved. From a taxonomic perspective SARS-CoV-2 is classified as a strain of the severe acute respiratory syndrome (SARS)-related coronavirus species.Coronaviruses are enveloped RNA viruses. The major surface protein is the large, trimeric spike glycoprotein (S) that mediates binding to host cell receptors as well as fusion of viral and host cell membranes. The S protein is composed of an N-terminal S1 subunit and a C-terminal S2 subunit, responsible for receptor binding and membrane fusion, respectively. Recent cryo-EM reconstructions of the CoV trimeric S structures of alpha-, beta-, and deltacoronaviruses revealed that the S1 subunit comprises two distinct domains: an N-terminal domain (S1 NTD) and a receptor-binding domain (S1 RBD). SARS-CoV-2 makes use of its S1 RBD to bind to human angiotensin-converting enzyme 2 (ACE2).The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health priority. Since the novel SARS-CoV-2 virus was first observed in humans in late 2019, over 8 million people have been infected and hundreds of thousands have died as a result of COVID-19. SARS-CoV-2, and coronaviruses more generally, lack effective treatment, leading to a large unmet medical need. In addition, there is currently no vaccine available to prevent coronavirus induced disease (COVID-19). The best way to prevent illness currently is to avoid being exposed to this virus. Since emerging infectious diseases, such as COVID-19 present a major threat to public health there is an urgent need for novel vaccines that can be used to prevent coronavirus induced respiratory disease.Wuhan coronavirus (2019-nCoV; also referred to as SARS-CoV-2) is a coronavirus that is responsible for an unprecedented current epidemic in China. 2019-nCoV is known to cause respiratory symptoms and fever, which may result in death. The World Health Organization declared the 2019-nCoV outbreak a Public Health Emergency of International Concern on January 30, 2020 and has confirmed over 11,000 cases in 16 countries. While the rapid development of a safe and effective 2019-nCoV vaccine is a global health priority, very little is currently known about 2019-nCoV immunology and mechanisms of immune protection.Accordingly, there is an unmet need in the field for 2019-nCoV therapies.SUMMARY OF THE INVENTIONIn the research that led to the present invention certain stabilized SARS-CoV-2 S proteins were constructed that were demonstrated to be useful as immunogens for inducing a protective immune response against SARS-CoV-2.The invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a 2019-NCOV Spike (S) protein (also referred to as SARS-CoV-2 S protein herein) comprising the following modifications to the full-length amino acid sequence of SEC ID NO: 29: a. stabilising mutations to proline at amino acids 986 and 987; and b. mutations to the furin cleavage site (SEC ID NO: 90).In some embodiments, these are the only modifications made to the sequence of SEC ID NO: 29. In other embodiments, the isolated nucleic acid molecule encodes a 2019-NCOV Spike (S) protein that comprises the following further modification to the full-length amino acid sequence of SEC ID NO: 29: c. deletion of the signal sequence.In some embodiments, the nucleic acid encoding the 2019-NCOV Spike (S) protein is operably linked to a cytomegalovirus (SEQ ID NO: 219) promoter, preferably the CMV immediate early promoter. In some embodiments, the nucleic acid encoding the 2019-NCOV Spike (S) protein is operably linked to a cytomegalovirus (CMV) promoter comprising at least one tetracycline operator (TetO) motif. In specific embodiments, the CMV promoter comprising at least one TetO motif comprises a nucleotide sequence of SEQ ID NO: 219. In some embodiments, the CMV promotor consists of the nucleotide sequence of SEQ ID NO: 219. These nucleic acids typically form part of a vector.In one aspect, the present invention thus relates to isolated and/or recombinant nucleic acids encoding a stabilized coronavirus S protein, in particular a SARS-CoV-2 S protein, said nucleic acids comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 211- 218, or fragments thereof. In a preferred embodiment, the present invention relates to an isolated and/or recombinant nucleic acid encoding a stabilized coronavirus S protein, in particular a SARS-CoV-2 S protein, said nucleic acid comprising a nucleotide of SEQ ID NO: 211, or fragments thereof.The invention provides an isolated 2019-NCOV Spike (S) protein (also referred to as SARS- CoV-2 S protein herein) comprising the following modifications to the full-length amino acid sequence of SEQ ID NO: 29: a. stabilising mutations to proline at amino acids 986 and 987; and b. mutations to the furin cleavage site (SEQ ID NO: 90).In some embodiments, these are the only modifications made to the sequence of SEQ ID NO: 29. In other embodiments the isolated 2019-NCOV Spike (S) protein comprises the following further modification to the full-length amino acid sequence of SEQ ID NO: 29: c. deletion of the signal sequence.In another aspect the invention relates to isolated and/or recombinant coronavirus S proteins comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 205-210, or fragments thereof, as well as to nucleic acids encoding such coronavirus S proteins, or fragments thereof.In a preferred embodiment, the invention relates to an isolated and/or recombinant coronavirus S proteins comprising an amino acid sequence of SEQ ID NO: 205, or fragments thereof, as well as to nucleic acids encoding such coronavirus S proteins, or fragments thereof.In yet another aspect, the invention relates to vectors comprising such nucleic acids. In certain embodiments, the vector is a recombinant human adenovirus of serotype 26.In another aspect, the invention relates to compositions and vaccines comprising such nucleic acids, proteins and/or vectors.In another aspect, the invention relates to methods for vaccinating a subject against COVID-19, the method comprising administering to the subject a vaccine or composition according to the invention.In another aspect, the invention relates to an isolated host cell comprising a recombinant human adenovirus of serotype 26 comprising nucleic acid encoding a SARS-CoV-2 S protein or fragment thereof.In another aspect, the invention relates to methods for making a vaccine against COVID-19, comprising providing a recombinant human adenovirus of serotype 26 that comprises nucleic acid encoding a SARS-CoV-2 S protein or fragment thereof, propagating said recombinant adenovirus in a culture of host cells, isolating and purifying the recombinant adenovirus, and formulating the recombinant adenovirus in a pharmaceutically acceptable composition. The recombinant human adenovirus of this aspect may be any of the adenoviruses described herein.In another aspect, the invention relates to an isolated recombinant nucleic acid that forms the genome of a recombinant human adenovirus of serotype 26 that comprises a nucleic acid encoding a SARS-CoV-2 S protein or fragment thereof. The adenovirus may also be any of the adenoviruses as described in the embodiments above.The invention also relates to a composition for use in prevention of molecularly confirmed, moderate to severe/critical COVID-19 in a subject in need thereof, comprising administering to the subject a composition or immunogenic composition of the invention as described herein, wherein the composition is administered at a dose of 5x1010 vp per dose in a one dose regimen (i.e. a single dose).The present invention features optimized and/or non-naturally occurring coronavirus (e.g., 2019- nCoV) nucleic acid molecules and polypeptides for the generation of DNA or RNA vaccines, antibodies, and immunogenic compositions and their use in methods of preventing, reducing and/or treating a coronavirus (e.g., 2019-nCoV) infection in a subject (e.g., a mammalian subject (e.g., a human)).One aspect of the invention features an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide having at least 85% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 1-84. In some embodiments, a) the polypeptide is capable of eliciting an immune response in a subject; or b) the polypeptide has at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to, or the polypeptide sequence of, any one of SEQ ID NOs: 1-84. In some embodiments, the polypeptide has the amino acid sequence of SEQ ID NO: 56. In some embodiments, the polypeptide has the amino acid sequence of SEQ ID NO: 51.Another aspect features an isolated nucleic acid molecule comprising a nucleotide sequence having at least 85% sequence identity to all or a portion of any one of SEQ ID NOs: 93-181 , 190-195, and 199-204, or a complementary sequence thereof. In some embodiments, the nucleic acid molecule has at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to, or the nucleotide sequence of, any one of SEQ ID NOs: 93-181, 190-195, and 199-204. In some embodiments, the nucleic acid molecule, or a portion thereof, is capable of eliciting an immune response in a subject. In some embodiments, the nucleic acid molecule has the nucleotide sequence of SEQ ID NO: 195. In some embodiments, the nucleic acid molecule has the nucleotide sequence of SEQ ID NO: 143. In some embodiments, the nucleic acid molecule has the nucleotide sequence of SEQ ID NO: 204. In some embodiments, the nucleic acid molecule has the nucleotide sequence of nucleotides 19-3837 of SEQ ID NO: 204. Another aspect features an isolated polypeptide comprising an amino acid sequence having at least 85% sequence identity to all or a portion of any one of SEQ ID NOs: 1-84. In some embodiments, said polypeptide has at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to, or the amino acid sequence of, any one of SEQ ID NOs: 1-84. In some embodiments, the polypeptide, or a portion thereof, is capable of eliciting an immune response in a subject. In some embodiments, the polypeptide has the amino acid sequence of SEQ ID NO: 28. In some embodiments, the polypeptide has the amino acid sequence of SEQ ID NO: 51.Another aspect features an isolated vector comprising one or more of the above nucleic acid molecules. In some embodiments, the vector is replication-defective (e.g., lacking an E1, E3, and/or E4 region). In some embodiments, the vector is a mammalian, bacterial, or viral vector.In some embodiments, the vector is an expression vector. In some embodiments, the viral vector is a virus selected from the group consisting of a retrovirus, adenovirus, adeno- associated virus, parvovirus, coronavirus, negative strand RNA viruses, orthomyxovirus, rhabdovirus, paramyxovirus, positive strand RNA viruses, picornavirus, alphavirus, double stranded DNA viruses, herpesvirus, Epstein-Barr virus, cytomegalovirus, fowlpox, and canarypox. In some embodiments, the vector is an adenovirus. In some embodiments, the adenovirus is selected from the group consisting of Ad2, Ad5, Ad11, Ad12, Ad24, Ad26, Ad34, Ad35, Ad40, Ad48, Ad49, Ad50, Ad52, Ad59, and Pan9. In some embodiments, the Ad52 is a rhesus Ad52 or the Ad59 is a rhesus Ad59. In some embodiments, the adenovirus is Ad26. In other embodiments, the adenovirus is an Ad26 vector that comprises a nucleic acid molecule with nucleotides 19-3837 of SEQ ID NO: 204 or all of the nucleotides of SEQ ID NO: 204. In another embodiment, the adenovirus is an Ad26 vector that comprises a nucleic acid molecule encoding a polypeptide with at least 85% or more (e.g., 90%, 95%, 99%, or 100%) sequence identity to the polypeptide of SEQ ID NOL 51.Another aspect features an isolated antibody that specifically binds to any of the abovementioned polypeptides. In some embodiments, the antibody is generated by immunizing a mammal with the nucleic acid, the polypeptide, or the vector. In some embodiments, the mammal is a human, cow, goat, mouse, or rabbit. In some embodiments, the antibody is humanized. In some embodiments, the antibody is an IgG. In some embodiments, the antibody is a bis-Fab, Fv, Fab, Fab’-SH, F(ab’)2, a diabody, a linear antibody, or a scFV. Another aspect features a method of producing an anti-2019-Wuhan coronavirus (2019-nCoV) antibody, comprising administering an amount of the nucleic acid molecule, the polypeptide, and/or the vector to a subject sufficient to elicit the production of neutralizing anti-2019-nCoV antisera after administration to said subject.Another aspect features an isolated anti-2019-nCoV antibody produced by any of the abovementioned methods. In some embodiments, the antibody binds to an epitope within any one of SEQ ID NOs: 1-84.Another aspect features a composition comprising the nucleic acid molecule, the polypeptide, the vectors or the antibody. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier, excipient, or diluent. In some embodiments, the composition further comprises an adjuvant or an immunostimulatory agent.Another aspect features an immunogenic composition comprising the nucleic acid molecule, the polypeptide, the vector, or the antibody. In some embodiments, the immunogenic composition is a vaccine. In some embodiments, the immunogenic composition is capable of treating or reducing the risk of a coronavirus infection (e.g., a 2019-nCoV infection) in a subject in need thereof. In some embodiments, the immunogenic composition elicits production of neutralizing anti-2019-nCoV antisera after administration to said subject. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the human has an underlying health condition. In some embodiments, the underlying health condition is hypertension, diabetes, or cardiovascular disease.Another aspect features a method of identifying, diagnosing, and/or predicting the susceptibility of a subject to a coronavirus infection comprising determining whether the subject has a protective level of an anti-coronavirus antibody (such as an anti-Spike antibody) in a sample from the subject, wherein preferably the protective level is: (i) a level that is at or above a titer of at least about 70, as determined using a pseudovirus neutralization assay; (ii) a level that is at or above a titer of at least about 25, as determined using a live virus neutralization assay; or (iii) a level that is at least 80% of a median level of an anti-coronavirus antibody in a cohort of convalescent humans, as determined by a pseudovirus neutralization assay or live virus neutralization assay. In some embodiments the protective level of an anti-coronavirus antibody is a level sufficient to prevent or reduce the development of severe disease. In some embodiments, the method further comprises administering an effective amount of the composition or the immunogenic composition to the subject having less than a protective level of the anti-coronavirus antibody. In some embodiments, the method further comprises identifying a subclass and/or an effector function of the anti-coronavirus antibody (e.g., the anti- Spike antibody). In some embodiments, the subclass is IgM, IgA, lgG1, lgG2, lgG3, or FcgR2A. In some embodiments, the effector function is antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent monocyte cellular phagocytosis (ADCP), or antibody-dependent NK cell activation. In some embodiments, the sample is a bodily fluid from the subject, wherein preferably the bodily fluid is blood. In some embodiments, the coronavirus is 2019-nCoV.Another aspect features a method of treating or reducing the risk of a coronavirus infection in a subject in need thereof, comprising administering a therapeutically effective amount of the composition or the immunogenic composition to said subject. In some embodiments, the method further comprises measuring an anti-coronavirus antibody (e.g., an anti-Spike antibody) level in the subject. In some embodiments, the anti-coronavirus antibody level in the subject is measured before and/or after the administration. In some embodiments, the anti-coronavirus antibody level in the subject is measured one or more times over about 1, 2, 3, 4, 5, or 6 days, 1, 2, 3, 4, 5, 6, or 7 weeks, 2, 3, 4, 5, or 6 months, 1, 2, 3, 4, or 5 years after administration. In some embodiments, the anti-coronavirus antibody level of the subject is below a protective level and wherein the method further comprises re-administering the composition or the immunogenic composition or administering a different anti-coronavirus composition to the subject. In some embodiments, the protective level is a level sufficient to reduce symptoms or duration of a coronavirus-mediated disease. In some embodiments, the protective level is a level sufficient to prevent or reduce the development of severe disease (e.g., which can be characterized by weight loss (e.g., a weight reduction of at least about 5% (e.g., at least about 7.5%, at least about 10%, at least about 12.5%, at least about 15%, at least about 20%, at least about 25% or more) relative to the subject’s initial weight pre-infection), the development of pneumonia and/or respiratory failure, and/or increased risk of death). In some embodiments, the protective level is: (i) a level that is at or above a titer of at least about 70, as determined using a pseudovirus neutralization assay; (ii) a level that is at or above a titer of at least about 25, as determined using a live virus neutralization assay; or (iii) a level that is at least 80% of a median level of an anti-coronavirus antibody in a cohort of convalescent humans, as determined by a pseudovirus neutralization assay or live virus neutralization assay. In some embodiments, the coronavirus is 2019-nCoV. In some embodiments, the method further includes measuring the coronavirus (e.g., 2019-nCoV) viral load in a sample from the subject. In some embodiments, the sample is a bronchoalveolar lavage (BAL) or a nasal swab (NS). In some embodiments, the sample is a bodily fluid (e.g., blood, e.g., whole blood or plasma) from the subject. In some embodiments, the sample is a tissue sample (e.g., a respiratory tract tissue sample) from the subject. In some embodiments, viral load is a detectible nucleic acid (e.g., subgenomic mRNA) level or a detectible protein (e.g., nucleocapsid protein (N)) level. In some embodiments, the detectible nucleic acid (e.g., subgenomic mRNA) is determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, LAMP, microarray analysis, or hybridization (e.g., ISH (e.g., FISH)). In some embodiments, the detectible protein (e.g., nucleocapsid protein (N)) is determined by an immunoassay (e.g., an immunohistochemical (IHC) assay or a lateral flow immunoassay). In some embodiments, a detectable viral load indicates that the subject is susceptible to disease (e.g., a 2019-nCoV-mediated disease, e.g., COVID-19, e.g., severe COVID-19 disease). In some embodiments, a viral load of greater than at least about 3.5 logio sgmRNA copies/mL. In some embodiments, a viral load of greater than 3.85 logio sgmRNA copies/mL in BAL or 3.78 logio sgmRNA copies/mL in NS indicates that the subject is susceptible to disease (e.g., a 2019- nCoV-mediated disease, e.g., COVID-19, e.g., severe COVID-19 disease). In some embodiments, a viral load of greater than 3.85 logio sgmRNA copies/mL in BAL or 3.78 logio sgmRNA copies/mL in NS indicates that the subject is susceptible to severe COVID-19 disease. In some embodiments, a viral load of greater than about 2.0 logio sgmRNA copies/g of tissue indicates that the subject is susceptible to severe COVID-19 disease. In some embodiments, a viral load of greater than about 8.0 logio sgmRNA copies/g in lung tissue, about 7.0 logio sgmRNA copies/g in nares tissue, about 6.0 logio sgmRNA copies/g in trachea tissue, about 5.5 logio sgmRNA copies/g in heart tissue, or about 2.0 logio sgmRNA copies/g in Gl, spleen, liver, kidney, or brain tissue indicates that the subject is susceptible to severe COVID-19 disease. In some embodiments, a viral load of greater than about 3% SARS-CoV-2 vRNA staining by ISH indicates that the subject is susceptible to disease. In some embodiments, a viral load of greater than about 5% SARS-CoV-2 vRNA staining by ISH indicates that the subject is susceptible to severe COVID-19 disease. In some embodiments, coronavirus (e.g., 2019- nCoV) viral load is measured one or more times over about 1, 2, 3, 4, 5, or 6 days or 1 , 2, 3, 4,5, 6, or 7 weeks post-infection. In some embodiments, a subject determined to be susceptible to disease (e.g., a 2019-nCoV-mediated disease, e.g., COVID-19, e.g., severe COVID-19 disease) is administered the composition or the immunogenic composition of the present disclosure alone or in combination with an additional therapeutic agent.Another aspect features a method of reducing a coronavirus-mediated activity (e.g., 2019- nCoV-mediated activity) in a subject infected with a 2019-nCoV, comprising administering a therapeutically effective amount of the composition or the immunogenic composition to said subject. In some embodiments, the therapeutically effective amount is sufficient to produce a log serum anti-Spike antibody titer greater than 2 in a subject, as measured by an ELISA assay. In some embodiments, the therapeutically effective amount is between 15 pg and 300 pg of the composition or the immunogenic composition. In some embodiments, the activity is viral titer, viral spread, infection, or cell fusion. In some embodiments, the viral titer is decreased after administration of the composition or the immunogenic composition. In some embodiments, the viral titer is decreased by 25% or more. In some embodiments, the viral titer is decreased by 50% or more. In some embodiments, the viral titer is decreased by 75% or more. In some embodiments, the coronavirus is undetectable after said administration. In some embodiments, the administering occurs prior to exposure to the coronavirus. In some embodiments, the administering occurs at least 1 hour prior to exposure to said coronavirus. In some embodiments, the administering occurs at least 1 week, 1 month, or a year prior to exposure to said coronavirus. In some embodiments, the administering occurs post-exposure to the coronavirus. In some embodiments, the administering occurs at least 15 minutes post-exposure to said coronavirus. In some embodiments, the administering occurs at least 1 hour, 1 day, 1- week, post-exposure to said coronavirus. In some embodiments, the subject is administered at least one dose of the nucleic acid molecule, polypeptide, vector, composition, immunogenic composition, and antibody. In some embodiments, the subject is administered at least two doses. In some embodiments, the nucleic acid molecule, polypeptide, vector, composition, or immunogenic composition is administered to said subject as a prime, a boost, or as a prime boost. In some embodiments, the nucleic acid molecule, polypeptide, vector, composition, immunogenic composition, or antibody is administered intramuscularly, intravenously, intradermally, percutaneously, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctivelly, intravesicularlly, mucosally, intraperi cardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, by catheter, by lavage, by gavage, in creams, or in lipid compositions. In some embodiments, the nucleic acid molecule, polypeptide, vector, composition, immunogenic composition, or antibody is administered intramuscularly. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the human has an underlying health condition. In some embodiments, the underlying health condition is hypertension, diabetes, or cardiovascular disease. In some embodiments, the method promotes an immune response in said subject. In some embodiments, the immune response is a humoral immune response. In some embodiments, the humoral immune response is an IgG response. Another aspect features a composition for use in treating or reducing the risk of a coronavirus infection, such as a 2019-nCoV infection, in a subject in need thereof, comprising a therapeutically effective amount of the composition or the immunogenic composition.Another aspect features a composition for use in reducing a coronavirus-mediated activity (e.g., 2019-nCoV-mediated activity) in a subject infected with a 2019-nCoV, comprising a therapeutically effective amount of the composition or the immunogenic composition.Another aspect features a method of manufacturing an immunogenic composition for treating or reducing the risk of a coronavirus (e.g., 2019-nCoV) infection in a subject in need thereof, said method comprising the steps of: (a) admixing at least one of the nucleic acid molecule, the polypeptide, the vector, the composition, and the antibody with a pharmaceutically acceptable carrier, excipient, or diluent to form the immunogenic composition; and (b) placing the immunogenic composition in a container.Another aspect features a kit comprising: (a) a first container comprising at least one of the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, and the antibody; (b) instructions for use thereof; and optionally (c) a second container comprising a pharmaceutically acceptable carrier, excipient, or diluent. In some embodiments, the first container further comprises a pharmaceutically acceptable carrier, excipient, or diluent. The kit optionally includes an adjuvant and/or an immunostimulatory agent.Another aspect features a kit comprising: one or more reagents for determining the presence of an anti-coronavirus antibody (such as an anti-Spike antibody) in a sample (e.g., a blood sample) from a subject and instructions for identifying, diagnosing, and/or predicting the susceptibility of a subject to a coronavirus infection. In some embodiments, the kit further comprises reagents for identifying a subclass and/or an effector function of the anti-coronavirus antibody. In some embodiments, the kit further comprises standards or samples for comparison.BRIEF DESCRIPTION OF THE DRAWINGSThe accompanying drawings are included to illustrate embodiments of the invention and further an understanding of its implementations. The foregoing summary, as well as the following detailed description of the invention, will be better understood when read in conjunction with the appended drawings. It should be understood that the invention is not limited to the precise embodiments shown in the drawings. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.FIG. 1 is a diagram showing Spike protein immunogens. Annotated domains of 2019-nCoV Spike (SEQ ID NO: 1) including the S1 (SEQ ID NO: 4), S2 (amino acids 665-1191 of SEQ ID NO: 1), TM (SEQ ID NO: 86), and CT (SEQ ID NO: 85) domains. Full-length Spike (SEQ ID NO: 1), SdCT (SEQ ID NO: 2), S.Ecto (SEQ ID NO: 3), S1-foldon (SEQ ID NO: 9), RBD-foldon (SEQ ID NO: 10), and S.Ecto-PP-foldon (SEQ ID NO: 22) protein immunogens are labeled. White boxes indicate foldon domain and the double intersecting lines in S.Ecto-PP-foldon indicate the approximate position of two stabilizing mutations (proline substitutions corresponding to amino acids K969 and V970 of SEQ ID NO: 1).FIG. 2 is a western blot showing the recognition of recombinant 2019-nCoV proteins by polyclonal anti-SARS antiserum. Cell lysates (left panel) and supernatants (right panel) from cells transfected with DNA encoding SS-Spike (lane 1), SS-SdCT (lane 2), SS-S.Ecto (lane 3), and SS-S.Ecto-dF-PP-foldon (lane 4) were probed using polyclonal anti-SARS antiserum. Numbered black lines to the left of each blot indicate approximate molecular weight in kDa and numbers at the top of each blot indicate lane number.FIG. 3 is a graph showing the recognition of full-length Spike by antibodies produced in 2019-nCoV vaccinated mice. Serum was collected from mice 4-weeks post-vacci nation with DNA encoding SS-Spike (lane 1), SS-SdCT (lane 2), SS-S.Ecto (lane 3), SS-S1-foldon (lane 4), SS-RBD-foldon (lane 5), and SS-S.Ecto-dF-PP-foldon (lane 6) and used in an ELISA with full- length Spike (SEQ ID NO: 1). Gray bars represent mean ELISA titer.FIG. 4 is a graph showing the recognition of S.dTM.PP by antibodies produced in 2019- nCoV vaccinated mice. Serum was collected from mice 4-weeks post-vaccination with DNA encoding SS-Spike (lane 1), SS-SdCT (lane 2), SS-S.Ecto (lane 3), SS-S1-foldon (lane 4), SS- RBD-foldon (lane 5), and SS-S.Ecto-dF-PP-foldon (lane 6) and used in an ELISA with full-length ectodomain S.Ecto-PP (SEQ ID NO: 19). Gray bars represent mean ELISA titer.FIG. 5 is a graph showing the neutralizing activity of antibodies produced in 2019-nCoV vaccinated mice. Serum was collected from mice 4-weeks post-vaccination with DNA encoding SS-Spike (lane 1), SS-SdCT (lane 2), SS-S.Ecto (lane 3), SS-S1-foldon (lane 4), SS- RBD-foldon (lane 5), and SS-S.Ecto-dF-PP-foldon (lane 6) and used in an in vitro 2019-nCoV Spike pseudovirus neutralization assay. Gray bars represent mean IC50 titer.FIGS. 6A-6E are graphs showing humoral immune responses in vaccinated rhesus macaques. Humoral immune responses were assessed following immunization by (FIG. 6A) binding antibody ELISA, (FIG. 6B) pseudovirus neutralization assays, and (FIG. 6C) live virus neutralization assays. (FIG. 6D) Comparison of pseudovirus neutralization titers in vaccinated macaques (all animals and SS-Spike / SS-SdCT groups), a cohort of 9 convalescent macaques, and a cohort of 27 convalescent humans from Boston who had recovered from 2019-nCoV infection. (FIG. 6E) S- and RBD-specific antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent monocyte cellular phagocytosis (ADCP), and antibody-dependent NK cell activation (IFN-y secretion, CD107a degranulation, and MIR-1b expression) are shown. Radar plots show the distribution of antibody features across the vaccine groups. The size and color intensity of the wedges indicate the median of the feature for the corresponding group (blue depicts antibody functions, red depicts antibody isotype/subclass/FcyR binding). The principal component analysis (PCA) plot shows the multivariate antibody profiles across groups. Each dot represents an animal, the color of the dot denotes the group, and the ellipses shows the distribution of the groups as 70% confidence levels assuming a multivariate normal distribution. Red bars reflect median responses. Dotted lines reflect assay limit of detection.FIGS. 7A-7B are graphs showing cellular immune responses in vaccinated rhesus macaques. Cellular immune responses were assessed following immunization by (FIG. 7 A) IFN-g ELISPOT assays and (FIG. 7B) multiparameter intracellular cytokine staining assays in response to pooled S peptides. Red bars reflect mean responses.FIGS. 8A-8D are graphs showing viral loads in 2019-nCoV challenged rhesus macaques.Rhesus macaques were challenged by the intranasal and intratracheal route with 1.2x1012 VP (1.1x104 PFU) 2019-nCoV. (FIG. 8A) Logio sgmRNA copies/mL or copies/swab (limit 50 copies/mL) were assessed in bronchoalveolar lavage (BAL) and nasal swabs (NS) in sham controls at multiple timepoints following challenge. (FIG. 8B) Logio sgmRNA copies/mL in BAL and (FIG. 8C) logio sgmRNA copies/swab in NS in vaccinated animals. (FIG. 8D) Peak viral loads in BAL and NS following challenge. Red lines reflect median viral loads. P-values indicate two-sided Mann-Whitney tests. FIGS. 9A-9C are graphs showing immune correlates of protection. Correlations of (FIG.9A) pseudovirus NAb titers and (FIG. 9B) live NAb titers prior to challenge with log peak sgmRNA copies/ L in BAL or log peak sgmRNA copies/swab in nasal swabs following challenge. Red lines reflect the best-fit relationship between these variables. P and R values reflect two-sided Spearman rank-correlation tests. (FIG. 9C) The heat map (top panel) shows the Spearman and Pearson correlations between antibody features and log peak sgmRNA copies/mL in BAL (*q