Henipavirus neutralizing monoclonal antibodies

Abstract

The disclosure provides a composition comprising at least two antibodies, wherein each antibody is a human or humanized antibody which binds to henipavirus F protein (an anti-henipavirus-F antibody).

Description

HENIPAVIRUS NEUTRALIZING MONOCLONAL ANTIBODIESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional patent application 63 / 662,861, filed on June 21, 2024 and is hereby incorporated by reference in its entirety.INCORPORATION BY REFERENCE OF AN ELECTRONIC SEQUENCE LISTING

[0002] This application contains a sequence listing that has been submitted in a computer readable format and is hereby incorporated by reference in its entirety. The computer readable file, created on June 14, 2025, is named 766527_MTST-312PC_SL.xml and is 6,060 bytes in size.BACKGROUND

[0003] Henipaviruses are enveloped, single-stranded RNA zoonotic viruses which can infect humans. Of the 6 identified Henipaviruses, Hendra virus (HeV) and Nipah (NiV) virus are highly virulent emerging pathogens that cause outbreaks in humans and are associated with high case-fatality ratios.

[0004] Hendra virus (HeV) infection is a rare emerging zoonosis (disease that can be transmitted to humans from animals) that causes severe and often fatal disease in both infected horses and humans. Nipah virus (NiV) is also a zoonotic virus and can also be transmitted through contaminated food or directly between people. In infected people, it causes a range of illnesses from asymptomatic (subclinical) infection to acute respiratory illness and fatal encephalitis. The virus can also cause severe disease in animals such as pigs, resulting in significant economic losses for farmers.

[0005] Although Nipah virus has caused only a few known outbreaks in Asia, it infects a wide range of animals and causes severe disease and death in people, with a fatality rate of 40-75%, making it a public health concern.

[0006] These viruses have high epidemic potential and are on the highest priority agents list for bioterrorism potential. It has been shown that anti-Henipavirus-F monoclonal antibodies protects subjects from NiVB in vivo. As such, there is priority to develop therapeutics and vaccines against henipaviruses.BRIEF SUMMARY

[0007] One aspect of the present disclosure is a composition comprising at least two antibodies, wherein each antibody is a human antibody or humanized antibody and binds to henipavirus F protein (an anti-henipavirus-F antibody).

[0008] In an aspect, each antibody is a monoclonal antibody.

[0009] In an aspect, each antibody comprises a VH3-33, VK3-11 clone.

[0010] In an aspect, the clone is selected from the group consisting of 2A1, 8G9, 2F7, 3H4, 6E1, or 9A6.

[0011] In an aspect, the composition is a therapeutic composition or a vaccine.

[0012] In an aspect, wherein the vaccine is a henipavirus, HeV and / or NiV vaccine.

[0013] In an aspect, wherein the composition is configured to be administered as an injectable preparation.

[0014] In an aspect, the composition further comprises one or more one or more therapeutically acceptable carriers, therapeutically acceptable diluents, therapeutically acceptable excipients or other therapeutic agents.

[0015] In an aspect, the therapeutically acceptable excipients are selected from the group consisting of salts, buffering agents, preservatives, antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, fillers, film formers, coatings, flavors, fragrances, glidants, lubricants, sorbents, suspending or dispersing agents, sweeteners, and waters of hydration.

[0016] One aspect of the disclosure is a method for immunizing a subject against an infection caused by henipavirus, HeV and / or NiV, comprising administering a therapeutically effective amount of the composition.

[0017] One aspect of the disclosure is a kit comprising the composition and instructions for use.

[0018] These and other advantages, aspects, and novel features of the present disclosure, as well as details of illustrated embodiments thereof, will be more fully understood from the following description and drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Various aspects of the present disclosure will now be described, by way of example only, with reference to the attached Figures, wherein:

[0020] FIG. 1 depicts protective epitopes and isolated NmAb against a broad range of HNF, proposing a combination of protective mAb in vivo.

[0021] FIG. 2A and 2B are graphs depicting panel of cross-neutralizing mAb targeting HNV F / RBP.

[0022] FIG. 3 shows the neutralization effect of clones according to an aspect of the disclosure

[0023] FIG. 4 depicts a 2A1 Fab complexed with sNiV-sF.

[0024] FIGs. 5A and 5B show how the 2A1 binding mechanism overcomes N67 glycan cap.

[0025] FIGs. 6A-6C depict how the 2A1 epitope is conserved among clinically important HNV.

[0026] FIGs. 7A and 7B show how 8G3 competes with sEphrin-B2 for NiV-RBS.

[0027] FIGs. 8 shows how 8G3 escape mutants are at NiV-RBS.

[0028] FIGs. 9A-9D show how 8G3 escape mutants are present in divergent African HNV.

[0029] FIGs. 10A and 10B are graphs showing that h8G3 cross-neutralize similarly both NiV and HeV.

[0030] FIGs. 11A and 11B show that a cocktail of h2Al and h8G3 to target both HNV glycoproteins simultaneously.

[0031] FIGs. 12A and 12B show that fully human h2Al and h8G3 protect hamsters from rNiVb.DETAILED DESCRIPTIONI. Introduction

[0032] Henipaviruses (HNVs), including Hendra (HeV) and Nipah (NiV) viruses, are highly pathogenic agents causing severe respiratory and neurological diseases in humans and animals. With case fatality rates ranging from 40% to >75%, and classification as biosafety level 4 (BSL-4) pathogens, these viruses pose a significant public health concern. Current vaccine and monoclonal antibody (mAb) candidates are targeted against closely related NiV and HeV. While promising, these narrowly focused approaches are insufficiently broad in their effectiveness, rendering them inadequate against increasingly diverse HNV clades.

[0033] The inventors aim to overcome this critical gap by developing antibodies against HNV fusion (F). This approach accounts for the existing diversity among HNVs and offers adevelopmental pipeline that could greatly enhance the approach to managing these highly pathogenic viruses. The outcomes will not only contribute to the immediate need for effective therapies but will also have broader implications for the field of antiviral countermeasures.II. Definitions

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the methods described herein belong. Any reference to standard methods refers to the most recent available version of the method at the time of filing of this disclosure unless otherwise indicated.

[0035] For any method disclosed herein that includes discrete steps, the steps may be conducted in any feasible order. And, as appropriate, any combination of two or more steps may be conducted simultaneously.

[0036] All headings are for the convenience of the reader and should not be used to limit the meaning of the text that follows the heading, unless so specified.

[0037] The words "preferred" and "preferably" refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the invention.

[0038] The term "comprises" and variations thereof do not have a limiting meaning where these terms appear in the description and claims. Such terms will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements.

[0039] By "consisting of' is meant including, and limited to, whatever follows the phrase "consisting of." Thus, the phrase "consisting of' indicates that the listed elements are required or mandatory, and that no other elements may be present. By "consisting essentially of' is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase "consisting essentially of' indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements.

[0040] The singular form "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. These articles refer to one or to more than one (i.e., to at least one). As used herein, the term "or" is generally employed in its usual sense including "and / or" unless the content clearly dictates otherwise. The term "and / or" means any one or more of the items in the list joined by "and / or". As an example, "x and / or y" means any element of the three-element set {(x), (y), (x, y)}. In other words, "x and / or y" means "one or both of x and y". As another example, "x, y, and / or z" means any element of the seven-element set {(x), (y), (z), (x, y), (x, z), (y, z), (x, y, z)}. In other words, "x, y and / or z" means "one or more of x, y and z".

[0041] Where ranges are given, endpoints include all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.). Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the disclosure, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. Herein, "up to" a number (for example, up to 50) includes the number (for example, 50). The term "in the range" or "within a range" (and similar statements) includes the endpoints of the stated range.

[0042] Reference throughout this specification to "one aspect,” "an aspect,” "certain aspects," or "some aspects," etc., means that a particular feature, configuration, composition, or characteristic described in connection with the aspect is included in at least one aspect of the disclosure. Thus, the appearances of such phrases in various places throughout this specification are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more aspects.

[0043] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." As used herein in connection with a measured quantity, the term "about" refers to that variation in the measured quantity as would be expected by the skilled artisan making the measurement and exercising a level of care commensurate with the objective of the measurement and the precision of the measuring equipment used. The term "about" as used in connection with a numerical value throughout the specification and the claims denotes an interval of accuracy, familiar and acceptable to a person skilled in the art. In general, such interval of accuracy is + / - 10%. Accordingly, unless otherwise indicated to the contrary, the numerical parameters set forth in the specification and claims areapproximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0044] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. All numerical values, however, inherently contain a range necessarily resulting from the standard deviation found in their respective testing measurements.

[0045] The term "exemplary" means serving as a non-limiting example, instance, or illustration. As utilized herein, the terms "e.g.," and "for example" set off lists of one or more non-limiting aspects, examples, instances, or illustrations.

[0046] As used herein, the term "substantially" refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. Biological and chemical phenomena rarely, if ever, go to completion and / or proceed to completeness or achieve or avoid an absolute result. The term "substantially" is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena. For example, "substantially" may refer to being within at least about 20%, alternatively at least about 10%, alternatively at least about 5% of a characteristic or property of interest.

[0047] A "disease", as used herein, is a state of health of a subject wherein the subject cannot maintain homeostasis, and wherein if the disease is not ameliorated, the subject's health continues to deteriorate. A "disorder" is a state of health in which the subject is able to maintain homeostasis, but in which the subject's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the subject's state of health. A “syndrome” is a recognizable complex of symptoms and physical findings that occur together and suggest the presence of a certain disease or disorder or an increased chance of developing the disease or disorder. A disease, disorder, or syndrome is "alleviated" if the severity of a sign or symptom of the disease, disorder, or syndrome, or the frequency with which such a sign or symptom is experienced by a subject, or both, is reduced.

[0048] As used herein, the terms “subject”, “individual”, and “patient” are interchangeable, and relate to vertebrates, preferably mammals. For example, mammals in the context of the disclosure are humans, non-human primates, domesticated animals such as dogs, cats, sheep,cattle, goats, pigs, horses, etc., laboratory animals such as mice, rats, rabbits, guinea pigs, etc., as well as animals in captivity such as animals in zoos. The term "animal" as used herein includes humans. The term "subject" may also include a patient, i.e., an animal, having a disease. In exemplary aspects, a subject, individual, or patient refers to a human (e.g., a man, a woman, or a child).

[0049] The terms “treat”, “treating”, or “treatment” refer to administering to a subject a compound or pharmaceutical composition disclosed herein to partially or completely alleviate, inhibit, ameliorate, or relieve the disease or disorder from which the subject is suffering. This means any manner in which one or more of the symptoms of a disease or disorder are ameliorated or otherwise beneficially altered. As used herein, amelioration of the symptoms of a particular disease or disorder refers to any lessening, whether permanent or temporary, lasting or transient, that can be attributed to or associated with treatment by the compounds, compositions, and methods of the present disclosure. For example, treating a subject can mean eliminating or reducing the clinical signs of a disease or disorder in the subject; arrest, inhibit, or slow the progression of the disease or disorder in the subject; and / or decrease the number, frequency, or severity of clinical symptoms and / or recurrence of the disease or disorder in the subject who currently has or who previously had the disease or disorder. In particular, the terms “treatment of a disease” and “treating a disease” include curing, shortening in duration, ameliorating, slowing down, inhibiting progression or worsening, or delaying the onset of clinical symptoms in a subject who has the disease or disorder.

[0050] The terms “prophylactic”, “preventive”, “preventing”, and “prevention” refer to a decrease in the occurrence of a disease or disorder, or a decrease in the risk of acquiring a disease or its associated symptoms in a subject. The prevention can be complete, e.g., the total absence of the disease or disorder) or partial, e.g., the occurrence of the disease or disorder in a subject is less than, occurs later than, or develops more slowly than that which would have occurred without the disclosed compounds, compositions, and methods.

[0051] As used herein, the term “preventing a disease” in a subject means, for example, to stop the development of one or more clinical symptoms of a disease or disorder in a subject before they occur or are detectable. Preferably, the disease or disorder does not develop at all, i.e., no symptoms of the disease or disorder are detectable. In some aspects, it can also mean delaying or slowing of the development of one or more symptoms of the disease or disorder. Alternatively, or in addition, it can mean decreasing the severity of one or more subsequently developed symptoms.

[0052] The term “administered” as used herein, means administration of an effective amount of a composition and / or any another other additional agent for treatment.

[0053] An "effective amount" includes a "therapeutically effective amount" and a "prophylactically effective amount." The term "therapeutically effective amount" refers to an amount effective in treating and / or ameliorating a disease or condition in a subject. The term "prophylactically effective amount" refers to an amount effective in preventing and / or substantially lessening the chances of a disease or condition in a subject.

[0001] As used herein “antibody” refers to a glycoprotein which exhibits binding specificity to a specific antigen. An antibody often comprises a variable domain and a constant domain in each of a heavy chain and a light chain. Accordingly, most antibodies have a heavy chain variable domain (VH) and a light chain variable domain (VL) that together form the portion of the antibody that binds to the antigen. Within each variable domain are three complementarity determining regions (CDR) which form loops in the heavy chain variable domain (VH) and light chain variable domain (VL) that contact the surface of the antigen. Antibodies herein also include intact molecules as well as functional fragments thereof, which are also referred to as an “antigen binding portion” or fragments of the antibody that are capable of binding to the antigen.

[0054] The invention is defined in the claims. However, below is a non- exhaustive listing of non-limiting exemplary aspects. Any one or more of the features of these aspects may be combined with any one or more features of another example, embodiment, or aspect described herein.III. Anti-Henipavirus-F human clonotypes

[0055] The development of human monoclonal antibodies (human mAb) for HNV disease is limited. Few patients have recovered from HMV disease and there is a lack of human mAB against HNV-F. The available mAbs do not cross-neutralize divergent HNV (as African HNV).

[0056] Henipavirus proteins include the attachment (G) protein, the fusion (F) protein and the phosphoprotein (P) gene products. The G protein of both HeV and NiV binds to ephrin B2, a conserved cell-surface glycoprotein that is widely distributed in vertebrates and is located preferentially in arterial endothelial cells and the surrounding tunica media, but is not found in venous endothelial cells. Ephrin B2 is also found in neurons, providing an explanation for virus growth in brain tissue and the occurrence of encephalitis in human patients.

[0057] The F protein is a type I membrane protein, and a biologically active form of the F protein is generated by the proteolytic cleavage of a protein precursor. It was recently found that the henipavirus F protein is cleaved by the endosomal protease cathepsin L, at a cleavage site that is unique among viral glycoproteins. The widespread distribution of the cathepsin L might also be crucial in the systemic spread of virus and the transmission of infectious virus within and between species.

[0058] The paramyxovirus P gene encodes three transcripts: the P, V and W proteins, each of which has a unique C-terminal domain and, compared with morbilliviruses and rubulaviruses, anN-terminal extension of 100-200 amino acids. P-gene products allow henipaviruses to evade host antiviral defenses by inhibiting both dsRNA signaling and interferon (IFN) signaling. Both the V and W proteins inhibit dsRNA signaling, but their distinct C-terminal domains enable them to do so in different cellular compartments; the W protein contains a nuclear-localization signal in the C-terminal domain. The P, V and W proteins also inhibit IFN signaling by targeting the STAT proteins in a novel strategy for paramyxoviruses that involves STATs being sequestered in high-molecular-weight complexes and, again, the W protein acts in the nucleus.

[0059] The present disclosure is directed to the generation and characterization of fully human mAbs against HNV, in particular antibodies that target henipavirus F protein (henipavirus-F). As depicted in FIG. 1, the inventors identified new protective epitopes and isolated NmAb against a broad range of HNF, proposing a combination of protective mAb in vivo.

[0060] As shown in FIG. 2, the inventors isolated a panel of cross-neutralizing mAb targeting HNV F / RBP. The mAb were isolated with hybridoma fusion. Screening was performed with HNVpp neutralization and flow cytometry surface binding staining.

[0061] IgSeq pipeline was used to analyze human germline usage. Germline usage and class enrichment was described. This included RNA extraction and cDNA synthesis (RACE) - Extracts were DNAse treated; RT primer (3’) binds CHI exon of IgG or IgK. Paired VH and VL PCR - Primer (3’) binds nested region in constant IgG or IgK; 5’ bind Universal sequence added during RACE reaction. The degree of SHM required for neutralization potency was also described. This included ONT barcoded library - 46 barcodes were ligated with ONT protocol V14 (SQK-NBD114.24). Bioinformatics to construct consensus - Two independent runs in MinlON were used; Consensus generated with Samtools (0.75 identity); Sanger sequencing was used for validation (VK).

[0062] VH3-33, VK3-11 was identified as a broadly neutralizing clonotype anti-HNV-F. As used herein, "VH3-33, VK3-11, CDRH3 13" refers to components of an antibody's variable region, specifically the heavy chain variable region (VH), light chain variable region (VK), and the complementarity determining region 3 (CDR3) of the heavy chain. VH3-33, refers to a specific gene or germline sequence encoding the variable region of the heavy chain (VH). It's associated with the induction of certain neutralizing antibodies (NAbs) against viral pathogens. VK3-11, refers to a specific gene or germline sequence encoding the variable region of the kappa light chain (VK). In the context of antibody structure, it is paired with the heavy chain variable region (VH) to form the complete antigen-binding site. CDRH3 13, refers to the length of the complementarity-determining region 3 (CDR3) of the heavy chain, specifically 13 amino acids. CDR3 is the most variable region of both the T-cell receptor (TCR) and immunoglobulin (Ig) and is crucial for antigen binding. The length and sequence of CDR3 are highly variable due to the mechanisms of V(D)J recombination, which generates diversity in the antibody repertoire. The CDR3 length in this case (13 amino acids) is within the range observed in some antibody repertoires.

[0063] Table 1 provides exemplary clones. Some of the clones of interest include, but are not limited to, 2A1, 8G9, 2F7, 3H4, 6E1, and 9A6. FIG. 3 shows the neutralization effect of the clones.

[0064] Table 1. Exemplary clones

[0065] As show in in FIG. 4, 2A1 recognizes conformationally apical NiV-F (stabilized prefusion, GCN trimerization motif) prefusion trimer. In particular, the Cryo-EM comprises 2A1 Fab complexed with sNiV-sF.

[0066] FIGs. 5A and 5B depict how the 2A1 binding mechanism also overcomes N67 glycan cap. Flow Cytometry surface binding on HEK293T transfected with HNV-F. Binding normalized to pRbb2489 and to NiV-F-WT.

[0067] FIGs. 6A-6C depict how the 2A1 epitope is conserved among clinically important HNV. FIG. 6B is a graph showing flow cytometry surface binding on HEK293T transfected with HNV-F.

[0068] FIGs. 7A and 7B show how 8G3 competes with sEphrin-B2 for NiV-RBS. GMFI was measured with flow cytometry and normalized to 8G3-488 binding without competitor; background (empty vector) was subtracted.

[0069] FIG. 8 shows how 8G3 escape mutants are at NiV-RBS and FIGs. 9A-9D show how 8G3 escape mutants are also present in divergent African HNV. FIG. 9C depicts flow Cytometry surface binding on HEK293T transfected with HNV-RBP. FIG. 9D is a 8G3 Fab docked on sNiV-RBP with Alphafold. Model overlapped on Cryo-EM NiV-RBP tetramer.

[0070] FIGs. 10A and 10B are graphs showing that h8G3 cross-neutralize similarly both NiV and HeV.

[0071] In some non- limiting aspects, at least two clones are formulated into a composition. In an aspect, the composition is a therapeutic composition. The therapeutic composition may optionally include one or more therapeutically acceptable carriers, diluents, or excipients such as salts, buffering agents, preservatives, antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, fillers, film formers or coatings, flavors, fragrances, glidants, lubricants, sorbents, suspending or dispersing agents, sweeteners, waters of hydration, and / or other therapeutic agents. As used herein, the term “excipient” means any pharmaceutically acceptable additive, carrier, diluent, adjuvant, or other ingredient, other than the active pharmaceutical ingredient (API) (and typically in addition to components of the delivery vehicle compositions), suitably selected with respect to the intended form of administration, and consistent with conventional pharmaceutical practices. The disclosed compounds can be administered to a subject or patient in a therapeutically effective amount. The complexes can be administered alone or as part of a pharmaceutically acceptable composition or formulation. In addition, the compositions can be administered all at once, as for example, by a bolus injection, multiple times, or delivered substantially uniformly over a period of time. It is also noted that the dose of the compound can be varied over time.

[0072] In some aspects, the composition is a therapeutic composition or a vaccine. A therapeutic composition or a vaccine may be referred to as a substance used to stimulate the production of antibodies and provide immunity against one or several diseases, prepared from the causative agent of a disease, its products, or a synthetic substitute. The therapeutic composition or vaccine may further comprise one or more immunologic adjuvants. As used herein, the term "immunologic adjuvant" refers to a compound or a mixture of compounds that acts to accelerate, prolong, enhance or modify immune responses when used in conjugation with an immunogen (e.g., neoantigens). Adjuvant may be non-immunogenic when administered to a host alone, but that augments the host's immune response to another antigen when administered conjointly with that antigen. Specifically, the terms "adjuvant" and "immunologic adjuvant" are used interchangeably in the present disclosure. Adjuvant- mediated enhancement and / or extension of the duration of the immune response can be assessed by any method known in the art including without limitation one or more of the following: (i) an increase in the number of antibodies produced in response to immunization with the adjuvant / antigen combination versus those produced in response to immunization with the antigen alone; (ii) an increase in the number of T cells recognizing the antigen or the adjuvant; and (iii) an increase in the level of one or more cytokines. Adjuvants may be aluminum based adjuvants including but not limiting to aluminum hydroxide and aluminum phosphate; saponins such as steroid saponins and triterpenoid saponins; bacterial flagellin and some cytokines such as GM-CSF. Adjuvants selection may depend on antigens, vaccines, and routes of administrations.

[0073] In some aspects, adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. Adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs). Adjuvants may be ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. In other instances, adjuvants may signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. In one example, the composition further comprises pidotimod as an adjuvant. In another example, the composition further comprises CpG as an adjuvant.

[0074] FIGs. 11A and 11B show that a cocktail of h2Al and h8G3 to target both HNV glycoproteins simultaneously. mAb anti-SARS-CoV2-Spike was used as isotype control.

[0075] FIGs. 12A and 12B show that fully human h2Al and h8G3 protect hamsters from rNiVb.

[0076] As disclosed above, the inventors were able to (i) isolate a panel of mAb targeting both HNV F and RBP using sequential immunization in H2L2 transgenic mice; (ii) isolated the first completely human mAb against HNV-F that is part of a clonotype, and we inferred the UCA and intermediates states during affinity maturation; (iii) use IgSeq to provide a description of human germline usage for mAb against HNV F; and (iv) show that the potent bNmAb h2Al and h8G3 protected hamsters from challenge with rNiVb. Further, the inventors propose h2Al+h8G3 as an additive cocktail to reduce the generation of escape mutant to monotherapy.

[0077] In some aspects, the disclosed compositions may be part of a kit. The kit may include a pharmaceutically acceptable carrier and / or a package insert comprising instructions for intratumoral administration (e.g., injection) of the therapeutic composition. The kit may also include additional therapeutic nucleic acids, drug, therapeutic agent, diagnostic agent, prophylactic agent, and / or any other agent that, when administered to a subject, has a therapeutic, diagnostic, and / or prophylactic effect and / or elicits a desired biological and / or pharmacological effect.

[0078] It will be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

CLAIMSWhat is claimed is:

1. A composition comprising at least two antibodies, wherein each antibody is a human antibody or humanized antibody and binds to henipavirus F protein (an anti- henipavirus-F antibody).

2. The composition of claim 1, wherein each antibody is a monoclonal antibody.

3. The composition of claim 1 or claim 2, wherein each antibody comprises a VH3-33, VK3-11 clone.

4. The composition of claim 3, wherein the clone is selected from the group consisting of 2A1, 8G9, 2F7, 3H4, 6E1, or 9A6.

5. The composition of any one of claims 1 to 4, wherein the composition is a therapeutic composition or a vaccine.

6. The composition of claim 5, wherein the vaccine is a henipavirus, HeV and / or NiV vaccine.

7. The composition of any one of claims 1 to 6, wherein the composition is configured to be administered as an injectable preparation.

8. The composition of any one of claims 5 to 7, wherein the composition further comprises one or more one or more therapeutically acceptable carriers, therapeutically acceptable diluents, therapeutically acceptable excipients or other therapeutic agents.

9. The composition of claim 8, wherein the therapeutically acceptable excipients are selected from the group consisting of salts, buffering agents, preservatives, antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, fillers, film formers, coatings, flavors, fragrances, glidants, lubricants, sorbents, suspending or dispersing agents, sweeteners, and waters of hydration.

10. A method for immunizing a subject against an infection caused by henipavirus, HeV and / or NiV, comprising administering a therapeutically effective amount of the composition of any one of claims 1 to 9.

11. A kit comprising the composition of any one of claims 1 to 9 and instructions for use.

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