Title of Invention	FULLY HUMAN MONOCLONAL ANTIBODIES AGAINST RABIES VIRUS AND USES THEREOF
Abstract	A fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucletide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO:1 and a light chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO:2

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FIELD OF INVENTION The present invention relates to human monoclonal antibodies against rabies virus and method of producing the human monoclonal antibodies BACK GROUND OF THE INVENTION Rabies is an acute zoonotic viral disease which infects domestic and wild animals. It is a neurological disease caused by infection of the central nervous system with rabies virus, a member of the Lyssavirus genus of the family Rhabdoviridae. It is transmitted to other animals and humans through close contact with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans. The first symptoms of rabies are usually non-specific and suggest involvement of the respiratory, gastrointestinal and/or central nervous systems. In the acute stage, signs of hyperactivity (furious rabies) or paralysis (dumb rabies) predominate. In both furious and dumb rabies forms complete paralysis occurs followed by coma and death in all cases, usually due to respiratory failure. Without intensive care, death occurs during the first seven days of illness. The rabies virus attacks nervous tissue and appears to replicate almost exclusively in neuronal cells. Once introduced through the skin or mucous membrane, the virus begins replicating in the striated muscles at the wound site. The virus can replicate in muscle cells for hours or weeks, or it can migrate immediately to the nervous system via unmyelinated sensory nerve endings at the inoculation site. Migration to the nervous system is via the nearest sensory or motor neuron in the ganglion at the base of the spinal cord or to the spinal cord itself. Once there, the virus continues to replicate. It can then be transported back to the wound site or to the brain via the central nervous system. Axonal transport to the CNS is at a rate of 3 mm per hour. It is possible however, that the virus also moves across cell-to-cell junctions and not just among nerve trunks. In the brain, the virus infects neurons in almost all brain regions, where it continues replication. Neuronal virus transmission from the periphery of the body to the brain is called "centripetal virus spread". Possible receptors for the virus are acetylcholine receptors, gangliosides and phospholipids. In aerosol transmission, the virus enters the body through the nasal epithelium and is subsequently transported to the olfactory bulb. It is thought that the virus replicates in the neurons of the olfactory bulb before spreading to other neurons in the brain. After the rabies virus infects the brain, it can continue to spread throughout the body via efferent neural pathways. At this stage, the virus can be found in salivary glands, taste buds, nasal cavities, tears, skin, the adrenal glands, pancreas, kidney, heart muscle, brown fat, hair follicles, retina, and cornea. The virus has never been detected in blood or blood cells. Almost invariably fatal, once clinical symptoms appear rabies can be averted by prompt treatment of an infected individual with a combination of passive and active immunization. Passive immunization consists of administration of pre¬formed rabies virus neutralizing antibodies obtained from pooled serum of rabies immune individuals (Human rabies-immune globulin; HRIG) or hyper-immunized horses (Equine rabies-immune globulin; ERIG). Both types of reagents present certain risks to recipients including variable antigen specificity and thus potency for different rabies virus isolates. Various attempts have been made for immunization against rabies virus. Monoclonal antibodies have been prepared using various strains of whole rabies virus. Production of Monoclonal antibodies against rabies has been disclosed in US patent no. 6,890,532. The invention provides Human monoclonal rabies virus neutralizing antibodies produced by fusion of Epstein-Barr Virus (EBV)-transformed, rabies specific human B cells with Mouse-human heterohybridoma. The two approaches that have been explored vigorously for production of monoclonal antibodies are transformation of B-cells by Epstein-Barr virus (EBV) and hybridization of B cells with drug-marked mouse or human myeloma or lymphoblastoma cell lines. Difficulties in establishing stable antibody-secreting clones have been a major problem with EBV transformation, and low frequency of hybrid clones resulting from fusion of human lymphocytes with human B-cells has limited progress with this approach to produce human monoclonal antibodies. Although fusion of human lymphocytes with mouse myeloma results in substantial numbers of hybrids secreting human IgG, there is a general feeling that these interspecies hybrids are rather unstable. (Cote et al. 1983) The Human monoclonal antibodies (huMabs) can be generated using either conventional hybridoma technology (Champion et al. 2000), phage display technology (Hoogenboom 2002), recombinant DNA technology (Chin et al. 2003) or transgenic mouse technology (Green 1999) or plant expression technology (Ko et al. 2004). The conventional strategies available for developing huMabs (human monoclonal antibodies) include protocols using Epstein Barr virus (EBV) to immortalize B cells from rabies-immune donors (Dietzschold, et al. 1990; Ueki et al. 1990; Dorfman, et al. 1994; Rando and Notkins 1994) with the additional step of fusing the obtained EBV-transformed human B lymphoblasts to one of the many fusion partner cell lines. Various fusion partner cell lines like mouse myeloma, SP2/0 (Enssle et al. 1991), human x mouse heteromyeloma cell lines, SHM-D33 (Champion et al. 2000), F3B6 (Ueki et al. 1990; Rando and Notkins 1994;), SPM 4-0 (Lafon et al. 1990) have been utilized for stabilizing EBV transformed B-lymphoblasts by back fusion. The transformation of human lymphocytes with EBV, however, results in a low rate of infection (Crawford et al. 1985) and successfully transformed cells tend to show unstable growth and secrete low levels of IgM antibody (Shay 1985). EBV transformation, to prepare the primary B-cells for fusion to reduce the likelihood of the heterohybrid cell lines expressing EBV antigens that may contaminate antibodies purified for human use. The use of heteromyelomas has been shown to hold more promise in the development of stable heterohybridomas than murine myelomas. A heteromyeloma cell line, K6H6/B5 (Carroll et al., 1986), produced from a fusion of P3/NSI/l-Ag4-1 cells with malignant cells from a human nodular lymphoma is known in the art. The K6H6/B5 cell line has been successfully used to clone human anti-viral monoclonal antibodies (Funaro et al., 1999; Siemoneit et al., 1994). There is a need to provide potent, inexpensive post-exposure treatments for humans which are useful against a variety of rabies virus strains. There is also a need for treatments which minimize risks of side effects. There is further need to produce an effective composition useful in post-exposure rabies treatments which are inexpensive and easy to produce in large volumes. SUMMARY OF THE INVENTION The present invention provides fully human monoclonal antibodies against rabies virus glycoprotein and a method of generating human monoclonal antibodies.. The invention also provides the nucleic acid and the polypeptide sequence of the heavy chain and light chain of the human monoclonal antibody. The invention further provides a kit for detection of rabies virus glycoprotein (RVGP) in a subject, wherein the kit comprises the human monoclonal antibodies disclosed in the present invention. In addition, the present invention provides a kit for passive immunization of a subject against rabies virus wherein said kit comprising the human monoclonal antibodies of the present invention. The antibodies provided in the present invention are used for Post-Exposure Prophylactic (PEP) treatment One aspect of the present invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 2. Another aspect of the present invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence having the nucleotide sequence as set forth in SEQ ID NO: 2. The invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide having amino acid sequence as set forth in SEQ ID NO: 3 and a light chain polypeptide encoded by a amino acid sequence as set forth in SEQ ID NO: 4. The invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7. Further, the invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 encoded by the nucleotide sequence as set forth in SEQ ID NO: 6 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7 encoded by the nucleotide sequence as set forth in SEQ ID NO: 5. Another aspect of the invention provides a pharmaceutical composition for passive immunization of a subject against rabies, wherein said composition comprising the monoclonal antibody as claimed in any of the proceeding claims. The invention provides a process of detecting rabies virus antigen in a sample, wherein the process comprising contacting at least a portion of said sample with a fiilly human monoclonal antibody as claimed in any of the proceeding claims; and determining the presence or absence of binding of said antibody to said antigen by conventional methods. The invention further provides a kit for passive immunization in a mammal against rabies, wherein the kit comprising the human monoclonal antibodies as claimed in any of the proceeding claims and an assay to determine the reaction of said antigen with said antibody. Additionally the invention provides a kit for detection of rabies virus antigen in a sample, wherein the kit comprising the human monoclonal antibodies as claimed in any of the proceeding claims and an assay to determine the reaction of said antigen with said antibody. DETAILED DESCRIPTION OF THE INVENTION The present invention provides fully human monoclonal antibodies against rabies virus glycoprotein and a method of generating human monoclonal antibodies. The invention also provides the nucleic acid and the polypeptide sequence of the heavy chain human monoclonal antibody. The invention further provides a kit for detection of rabies virus glycoprotein (RVGP) in a subject, wherein the kit comprises the human monoclonal antibodies disclosed in the present invention. In addition, the present invention provides. The antibodies provided in the present invention are used for Post-Exposure Prophylactic (PEP) treatment. The present invention relates to these monoclonal rabies virus neutralizing human antibodies, the nucleic acid sequences of their heavy and light chains and the amino acid sequences of the encoded proteins. Also provided in the present invention are methods of using the monoclonal antibodies as a therapeutically effective post-exposure prophylactic treatment of individuals exposed to rabies virus. The present invention provides fully monoclonal antibodies that bind specifically to the glycoprotein of various rabies virus strains. Post-exposure treatment with monoclonal antibody or a mixture of a variety of monoclonal antibodies neutralizes the rabies virus at the site of entry and prevents the virus from spreading to the central nervous system (CNS). Thus, for transdermal or mucosal exposure to rabies virus, rabies specific-monoclonal antibodies are instilled into the bite site, as well as administered systemically. Since viral replication is restricted almost exclusively to neuronal cells, neutralization and clearance of the virus by the monoclonal antibodies of the present invention prior to entry into the CNS is an effective post-exposure prophylactic treatment. The monoclonal antibodies against rabies virus disclosed are generated by B-cell immortalization mediated by a hetero-myeloma cell line, wherein the B cells are stimulated by miotgen. The present invention provides a method of generating human monoclonal antibodies against rabies virus glycoprotein, the major immunogenic surface protein known to harbor virus neutralizing epitopes. These RVhuMabs have been shown to have the potentials for effective post exposure prophylaxis (PEP) of human rabies especially by conferring passive immunity. In particular, the present invention provides heterohybridomas between rabies virus immune primary peripheral blood B-cells and a heteromyeloma cell line, K6H6/B5. These human monoclonal antibodies against rabies virus (RVhuMabs) are useful to replace polyclonal rabies immunoglobulin (RIG) of either equine (ERIG) or human (HRIG) origin, which are the RIG of choice for Post-Exposure Prophylaxis (PEP) of human rabies, because of their proven safety and efficacy. Human monoclonal antibodies disclosed in the present invention have been made by mitogen stimulated rabies virus-specific human B cells with mouse-human heterohybrid donors encoding the antibody comprising heavy and light chains having nucleotide sequence as set forth in SEQ ID NO: 1 and SEQ ID NO: 2. The use of mitogen stimulation is advantageous over the EBV transformation to prepare the primary B-cells for fusion as it reduces the likelihood of the heterohybrid cell lines expressing EBV antigens that may contaminate antibodies purified for human use. The term 'monoclonal antibody' (mAb) as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations which include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by the method known in the art such as hybridoma method, recombinant DNA methods and phage antibody library method. The term 'Fully human monoclonal antibodies (HumAb)' used herein refers to antibodies with 100% human protein sequences. A "neutralizing antibody" is an antibody molecule that is able to eliminate or significantly reduce an effector function of a target antigen to which it binds. "Neutralize," for purposes of treatment, means to partially or completely suppress chemical and/or biological activity. Unless specifically identified herein, "human" and "fully human" antibodies can be used interchangeably herein. The term "fully human" can be useful when distinguishing antibodies that are only partially human from those that are completely, or fully human. The term 'prophylactic' herein refers to a medication or a treatment designed and used to prevent a disease from occurring. "Prophylactic treatment" includes occurrences when a treatment decreases the likelihood a subject will become sick or increases the amount of time required for the subject to become sick or exhibit symptoms or conditions associated with the disorder. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment' of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. "Treatment" can also mean prolonging survival as compared to expected survival if not receiving treatment. Those in need of treatment include those already with the condition or disorder as well as those prone to have the condition or disorder or those in which the condition or disorder is to be prevented. One embodiment of the present invention is directed to a method of generating human monoclonal antibodies against rabies virus comprising stimulating the B cells isolated from human with the mitogen, immortalizing the stimulated human B cells by a human x mouse heteromyeloma cells and isolating and purifying the monoclonal antibodies. Another embodiment of the present invention relates to a method of generating rabies virus neutralizing fully human monoclonal antibodies comprising fusion of mitogen stimulated peripheral blood B cells and human-mouse heteromyeloma cell line K6H6/B5, wherein the B cells derived from human vaccinated with Pasteur virus (PV) strain of rabies virus. Yet another embodiment of the present invention relates to a method of generating rabies virus neutralizing fully human monoclonal antibodies comprising fusion of pokeweed mitogen stimulated peripheral blood B cells and human-mouse heteromyeloma cell line K6H6/B5, wherein the B cells derived from human vaccinated with Pasteur virus (PV) strain of rabies virus. One embodiment of the present invention relates to other mitogens such as phvtohacmagglutinin (PHA), concanavalin A (conA), lipopolvsaccharide (LPS), and pokeweed mitogen (PWM). In one embodiment relates to various fusion partner cell lines like mouse myeloma, SP2/0, SHM-D33, F3B6, SPM 4-0 can also be used for the generation of the RVhuMabs. One embodiment of the present invention is to provide nucleic acid molecule of monoclonal antibody disclosed in the present invention, wherein the monoclonal antibody comprises of heavy chain having nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain having nucleotide sequence as set forth in SEQ ID NO: 2. Further embodiment of the invention includes all the other DNA sequences which encode substantially the same or a functionally equivalent heavy and light chain amino acid sequences, is within the scope of the invention. Altered DNA sequences which may be used in accordance with the invention include deletions, additions or substitutions of different nucleotide residues resulting in a sequence that encodes the same, or a functionally equivalent, gene product. The gene product itself may contain deletions, additions or substitutions of amino acid residues within a heavy or light chain sequence which resuh in a silent change, thus producing a functionally equivalent monoclonal antibody. The heavy chain and light chain of the fully human monoclonal rabies virus neutralizing antibody specifically binds to a rabies virus protein. One embodiment of the present invention provides the polypeptide sequence of the heavy chain having amino acid as set forth in SEQ ID NO 3 and the polypeptide sequence of the light chain having amino acid as set forth in SEQ ID NO 4. The fully human monoclonal antibodies against rabies virus described in the present invention can be produced by recombinant DNA technology. One preferred embodiment of the present invention is directed to a process on geobtaining peripheral blood lymphocytes from a subject multiply vaccinated with the Abhayrab® purified Vero cell rabies vaccine (PVRV) which incorporates PV strain and PV strain has been reported to provide broad coverage against the rabies virus (RV) strains. Another embodiment of the present invention provides human monoclonal antibodies (RVhuMabs) specific to rabies virus glycoprotein that effectively neutralize various fixed and street rabies viruses (SRV) both in vitro and in vivo. In another embodiment of the invention invention a process for preparation of stable heterohybridomas secreting rabies virus specific human monoclonal antibodies. The fixed rabies virus strains are laboratory adapted rabies virus strains. The street rabies viruses are isolates from naturally infected animals. They were found to be efficacious in protecting Syrian hamsters and mice against rabies after severe exposure. The cell fusion between an antibody-producing cell and a myeloma cell can be achieved by the routine procedure for example chemical fusion mediated by poly ethylene glycol (PEG) and physical fiision mediated by electrical impulses (electro fusion). The invention provides a method for generating human monoclonal antibodies against rabies virus. Similarly this method can be used for generating monoclonal antibodies from other animals. The invention provides a method for generating human monoclonal antibodies against rabies virus. Similarly this method can be used for generating monoclonal antibodies against various other antigens. The RVhuMabs of the present invention have neutralizing activity suggesting their relevance against all SRVs of dog origin circulating in endemic regions such as of the Indian sub-continent. These antibodies can be used for passive immunotherapy of rabies post-exposure cases in other countries as well. One embodiment of the present invention provides a fiilly human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 2. Another embodiment of the present invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence having the nucleotide sequence as set forth in SEQ ID NO: 2. The invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide having amino acid sequence as set forth in SEQ ID NO: 3 and a light chain polypeptide encoded by a amino acid sequence as set forth in SEQ ID NO: 4. The invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7. Further, the invention provides a fully human monoclonal antibody against rabies comprising a heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 encoded by the nucleotide sequence as set forth in SEQ ID NO: 6 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7 encoded by the nucleotide sequence as set forth in SEQ ID NO: 5. Another embodiment of the invention provides a pharmaceutical composition for passive immunization of a subject against rabies, wherein said composition comprising the monoclonal antibody as claimed in any of the proceeding claims. The invention provides a process of detecting rabies virus antigen in a sample, said process comprising: contacting at least a portion of said sample with a fully human monoclonal antibody as claimed in any of the proceeding claims; and determining the presence or absence of binding of said antibody to said antigen by conventional methods. The invention further provides a kit for passive immunization in a mammal against rabies, comprising: the human monoclonal antibodies as claimed in any of the proceeding claims and an assay to determine the reaction of said antigen with said antibody. Additionally the invention provides a kit for detection of rabies virus antigen in a sample, said kit comprising the human monoclonal antibodies as claimed in any of the proceeding claims and an assay to determine the reaction of said antigen with said antibody. In another embodiment the invention provides a process for producing the fully human monoclonal antibodies as disclosed in the present invention, wherein the process comprises: obtaining plurality of B peripheral lymphocyte from human vaccinated with Pasteur virus (PV) strain of rabies virus; stimulating the lymphocytes with a miotogen to obtain stimulated lymphocytes; fusing the stimulated lymphocytes with plurality of human-mouse myeloma to obtain stable heterohybridoma; and isolating the monoclonal antibodies from the heterohybridoma Another embodiment of the present invention relates to the mitogens such as phytohaemagglutinin (PHA), concanavalin A (conA), lipopolysaccharide (LPS) and pokeweed mitogen (PWM). These mitogens can be used for the stimulation of B lymphocytes. The process for obtaining the fully human monoclonal antibodies as disclosed in the present invention, wherein the B cells were stimulated by using pokeweed mitogen (PWM). The present invention describes a method of preparation of rabies virus neutralizing human monoclonal antibodies involving fusion of mitogen stimulated immune peripheral blood B cells from subjects vaccinated with the Abhayrab® purified Vero cell rabies vaccine (PVRV) incorporating PV strain and K6H6/B5 cell line (human x mouse, heteromyeloma). Stable heterohybridomas were established after five rounds of single cell cloning stably secreted huMabs. Detailed procedure is explained in Example 1. The RVhuMabs were characterized to study the isotype, specificity, cross-reactivity, neutralizing ability in vitro and the ability to confer protection post¬exposure. All the RVhuMabs were of yl heavy chain and X light chain isotype. Their specificity to RV was demonstrated by a Cell-ELISA using unfixed mock and RV infected cell culture. All the RVhuMabs showed reactivity to all the fixed RVs except BHK adapted CVS strain. None of the RVhuMabs showed any reactivity to host cell protein. The RVhuMabs bound specifically to native form of whole virus antigens as well as purified RVGP and did not react with ribo-nucleoprotein (RNP) as evident from the results of Indirect ELISA. The RVhuMabs recognized antigenic site III of RVGP as determined by a competitive ELISA using a mouse monoclonal antibodies (Mab) (Dl) against antigenic site III. The RVhuMabs were tested for their ability to neutralize various street RVs and fixed RVs both in vitro and in vivo. The mouse neutralization test (MNT) was conducted in Swiss albino mice to demonstrate the ability of the RVhuMabs to neutralize street rabies viruses in vivo. All the RVhuMabs tested could neutralize all the four Indian street rabies viruses (SRVs) of dog origin in mouse neutralization test (MNT). All the RVhuMabs neutralized four fixed (PV, Flury LEP, SAD and CVS-II) RV while none of the huMabs neutralized baby hamster kidney (BHK) adapted challenge virus standard rabies virus (CVS RV) when tested by rapid fluorescent focus inhibition test (RFFIT). The RVhuMabs had RFFIT titers ranging from 2.5 lU to 13.5 lU. Based on the RFFIT titers, four RVhuMabs designated as RI6C9, RI6E5, RI6F7, R14D6were selected for further test for their ability to neutralize members of other Lyssavirus genotypes. All the four RVhuMabs i.e R16C9, R16E5, RI6F7, RI4D6 neutralized genotype 7 (GT7) (ABLV) and genotype 4 (GT4) (DUV) effectively while they did not neutralize genotype 3 (GT3) (MOKV) and genotype 5 (GT5) (EBLV-l) when tested by RFFIT. A comparative study was undertaken using the combination of vaccine and RVhuMabs (alone and in combination) as well as human rabies immunoglobulin (HRIG) in Syrian hamsters inoculated intramuscularly in gastrocnemius muscle with two SRV isolates. Both the huMabs R16F7 & RI4D6 could prevent the spread of rabies virus from the site of inoculation to central nervous system (CNS) and thus were able to protect all the hamsters while HRIG in combination with vaccine and vaccine alone were able to afford protection in 40 to 80% of the infected hamsters. All the eight RVhuMabs tested appear to have sufficient spectrum of neutralizing activity against Indian SRVs. Recent epidemiological study suggests that dogs are the primary reservoirs of rabies virus in India and that the circulating viruses belong to genotype 1 (Nagarajan et al., 2006). The RVhuMabs described in this invention are effective against SRVs of dog origin suggesting their relevance for use in rabies endemic regions especially of the Indian sub-continent. The present invention describes a method for making human hetero-hybridomas with out the need for transformation of human B lymphocytes. EXAMPLES It should be understood that the following examples described herein are for illustrative purposes only and that various modifications or changes in light will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims. Example 1 Preparation of human monoclonal antibodies Isolation of human peripheral B lymphocytes (PBLs) The human B cells were obtained from the peripheral blood of a donor 7 days after the third dose of primary rabies following administration of booster vaccine. In all cases the vaccine employed was Abhayrab® purified Vero cell rabies vaccine (PVRV) which incorporates PV strain which has been reported to provide broad coverage against the rabies virus (RV) strains (Badrane et al., 2001). All of the donors were negative in tests for HIV and hepatitis B. The mouse-human hybrid heteromyeloma cell line, K6H6/B5 produced from a fusion of P3/NSI/I-Ag4-l cells with malignant cells from a human nodular lymphoma (Carroll et al., 1986). Mitogen stimulation, rather than EBV transformation was used to prepare the primary B-cells for fusion to reduce the likelihood of the heterohybrid cell lines expressing EBV antigens that may contaminate antibodies purified for human use. Rabies Viruses To assess the capacity of antibody preparations to neutralize a variety of rabies virus strains, a number of antigenically distinct, fixed laboratory strains as well as four representative street rabies viruses (SRV) were used. The rabies virus Pasteur strain, L 2061 (PV) is a vaccine strain obtained from Institute Pasteur, Paris, France. Purified Vero cell derived rabies vaccine were obtained from the Human Biologicals Institute, Udhagamandalam, India., Street Alabama Dufferin (SAD) strain was obtained from Institute of Virology and Immunoprophylaxis, Mittelhausen, Switzerland, BHK cell culture adapted Flurry low-egg-passage strain (Flury LEP) strain was obtained from CZV, Esparia, Spain. The Challenge Virus Standard 11 (CVS 11) was obtained from Agence Francaise De Securite Sanitaire Des Aliments, Malzville, France, Baby hamster kidney cell line adapted challenge virus standard (CVS-BHK) was obtained from Indian Immunologicals Ltd, Hyderabad, India. Four Indian SRVs (designated as SRV 108, SRV 141, SRV 142 & SRV 129) isolated from brain samples of dogs died due to rabies were used. The rabies viruses from the dog brain samples were isolated by passage in mice as described elsewhere (Nagarajan et al., 2006). Mitogen stimulation of Human PBLs The human peripheral blood lymphocytes fractionated using Ficol-Hypaque were cultured in 24 well tissue culture plates and stimulated with pokeweed mitogen at a concentration of 5 fxg/ml. After 5 days of stimulation in vitro the cells were harvested and used as fusion partners. Example 2 Establishment and characterization of stable heterohybridomas The hetero-hybridomas were created by fusing harvested, mitogen stimulated peripheral blood lymphocytes with the hetero-myeloma at a ration of 1:1 and the resultant hybrids were plated in 96 well plates. The antibodies secreted by hetero¬hybridomas were screened using the indirect ELISA. Stable heterohybridomas secreting RV specific huMabs have been established after five rounds of rigorous single cell cloning. A total of fifteen clones were developed of which eight clones were selected for characterization namely R17D6, R17D6, R14B3, R16C9, R14D6, R18G9, R16F7, R17G9 and R16E5. These huMabs were characterized to study the isotype, specificity, cross-reactivity, neutralizing ability in vitro and the ability to confer protection post-exposure. All the huMabs were of yl heavy chain and X light chain isotype (Table 1). Example 3 Analysis of Rabies Virus-Specific Antibodies in ELISA The specificity of huMabs to RV was demonstrated by a Cell-ELISA using fixed mock and RV infected cell culture. Mouse neuroblastoma (MNA) cells grown in 96 well plates were infected with different rabies viruses, fixed and the rabies antigen was detected using the human monoclonal antibody secreted by the hetero¬hybridomas. All the huMabs showed reactivity to all the fixed RVs except BHK adapted CVS strain. None of the huMabs showed any reactivity to host cell protein. The huMabs bound specifically to native form of whole virus antigens as well as purified RVGP and did not react with RNP as evident from the results of Indirect ELISA. The huMabs recognized anfigenic site III of RVGP as determined by a Competitive ELISA using a mouse Mab (DI) against antigenic site III as described elsewhere (Nagarajan et al. 2005). Example 4 Rapid Fluorescent Focus Inhibition Test for Rabies (RFFIT) Monoclonal antibodies were mixed with CVS 11 (40 FFD50) and incubated for 90 minutes in Labtek 8-chamber slides (Nunc, Denmark). MNA cells were added to the mixture and incubated for 20 hours. Immunofluorescent foci were counted after acetone fixation and potency values were calculated based on comparison with an international reference serum (NIBSC, UK). The huMabs had RFFIT titers ranging from 2.5 lU to 13.5 lU. Based on the RPFIT titers, five huMabs were selected for further test for their ability to neutralize members of other Lyssavirus genotypes. All the four huMabs neutralized GT7 (ABLV) and GT4 (DUV) effectively while they did not neutralize GTS (MOKV) and GTS (EBLV-l) when tested by RFFIT. Details are provided in Table 1 and Table 2. Example 5 Mouse Neutralization Test (MNT)/Mouse protection test (MPT) Survivorship of Swiss albino mice subjected to mouse neutralization test to demonstrate the ability of human monoclonal antibodies to neutralize various fixed and street rabies viruses in vivo. The huMabs neutralized all the four Indian SRVs (108, 141, 142, & 129) of dog origin in mouse neutralization test (MNT). Three to four weeks old female Swiss albino mice were intracranialy inoculated with 30 nl of (50 MICLD50/3O ^1) either rabies virus infected culture fluid or brain homogenates from naturally infected rabid stray dogs. The inoculated mice were observed daily for symptoms typical of rabies for 21 days. The results are expressed as percentage of mice that survived after 21 days of observation. Details are provided in Table 1 and Table 3. Example 6 In vivo neutralization in Syrian hamsters A comparative study was undertaken using the combination of vaccine and huMabs (alone and in combination) as well as HRIG in Syrian hamsters inoculated intramuscularly in gastrocnemius muscle with two SRV isolates. Both the huMabs (R16F7 & R14D6) could prevent the spread of rabies virus from the site of inoculation to CNS and thus were able to protect all the hamsters while HRIG in combination with vaccine and vaccine alone were able to afford protection in 40 to 80% of the infected hamsters. The huMabs appear to have sufficient spectrum of neutralizing activity against Indian SRV. Recent epidemiological study suggests that dogs are the primary reservoirs of rabies virus in India and that the circulating viruses belong to genotype I (Nagarajan et al., 2006). Since the huMabs described in this invention are effective against street rabies viruses isolated from dogs suggesting their relevance for use in the Indian sub-continent. Example 7 Purification of antibodies Antibodies were purified using the affinity chromatography method using protein G. Cell culture supematants precipitated with ammonium sulphate were applied to protein G columns and the bound antibodies were eluted, characterized for protein concentration, isotype and specificity using the indirect ELISA method. Example 8 Extraction of total RNA and messenRer RNA (mRNA) preparation Trizol reagent (Invitrogen) was used for extraction of total RNA according to the manufacturers protocol. Briefly, 5-10 xlO^ cells were lysed by resuspension in 1 ml of Trizol reagent followed by incubation of these homogenized cells at 15-20°C for 5 min. 0.2 ml of chloroform (Merck) was added per ml of Trizol used followed by 15 seconds of vigorous shaking by hand and subsequent incubation for 2-3 min at 15-20°C. The samples were centrifuged for 15 min at 12000 g at 2-8 °C. The colorless aqueous phase containing the RNA was transferred to fresh tube and RNA precipitated by incubation with 0.5 ml of Isopropanol (Gibco BRL) per ml of Trizol followed by incubation at 15-20°C for 10 min and centrifugation (12000 g/10 min/ 2-3°C). The RNA containing pellet was washed once with 75 % Ethanol (Merck). The pellet was air dried for 5-10 min and redissolved in RNase free water (50-100 |jl) and followed by incubation for 10 min at 55-60°C. cDNA preparation and PCR amplification of second strand cDNA synthesis An RT-PCR kit (Qiagen, GmBH) was used according to the manufacturers protocol for amplification of first strand cDNA with primer pairs as described by Pope AR et al. The RT-PCR reagents was reconstituted in 40\i\ of RNase free water; 1^1 (lOpmol) of heavy or light chain specific primer (Pope AR et al In McCafferty J, Hoogenboom H and Chiswell D (Eds); Antibody Engineering: A practical approach; Oxford University Press; 1996 ppl-40) was added along with 20ng of freshly prepared mRNA. The reaction mix was incubated at 42°C for 30min followed by 5 min at 95°C, to inactivate the Reverse Transcriptase enzyme. Second strand cDNA was amplified using PCR reagents from Qiagen (Germany). Reaction conditions- 32 cycles X (95°C-1 min, 55°C- Imin, 72°C- 1 min), followed by 10 min at 72°C. 1/10* (5 nl) of the amplified product was checked on a 1.2 % Agarose gel. PCR products obtained from VH and VL amplification were cloned into TA cloning vector using TOPO-TA cloning kit and sequenced using T? forward and SPe Reverse primers. Table 1: Characterization of anti rabies virus huMabs S.No Clone Isoty Prot Antig ID pe em speci ficity enic site RFFIT (\V) MPT Survivorship (%) PV SAD CVS CVS Flury DRV DRV DRV PV CVSll 11 BHK adapte d LEP 108 (1:5 humab ) 141 (1:5 humab ) 142 (1:5) (1:5 humab ) (1:5 humab ) 1. R17D 6* G1,A, GP III 2.57 13.8 11.48 - 10 100 100 100 80 80 2. R14B3 * G1,X GP III 2.57 4.78 2.81 - 3.09 ND ND 80 ND ND 3. R16C 9* G1,X GP III 2.81 12.8 8 3.54 " 0.3 100 100 100 ND ND 4. R14D 6* G1,X GP III 0.79 2.81 1.62 - 1.25 lOO 100 60 ND 5. R18G 9* G1.X, GP III 2.81 12.8 8 5.24 " 8.12 100 100 0 100 ND 6. R16F7 * G1,X GP III 2.57 6.3 2.81 - 4.78 100 100 100 ND 80 7. R17G 9* Gl,>. GP III 2.57 2.81 2 - 3.01 lOO 100 100 ND ND 8. R16ES * GIA GP HI 0.67 2.81 2 - 2.57 60 100 80 100 100 * Neat Heterohybridoma spent medium. ND - Not done. * Neat Heterohybridoma spent medium. ND - Not done. Table 2: Neutralization of rabies viruses by anti-rabies virus human monoclonal antibodies S.No huMab" VNA' (lU/ml) Fixed IV strains PV CVS-11 SAD Flury LEP CVS-BHK 1 R17D6 2.6 11.5 13.8 10.0 - 2 R14B3 2.6 2.8 4.8 3.1 - 3 R16C9 2.8 3.5 12.9 0.3 - 4 R14D6 0.8 1.6 2.8 1.3 - 5 R18G9 2.8 5.2 12.9 8.1 - 6 R16F7 2.6 2.8 6.3 4.8 - 7 R17G9 2.6 2.0 2.8 3.0 - 8 R16E5 0.7 2.0 2.8 2.6 - ^ VNA titer was determined by RFFIT using rabies virus strain CVS-11 essentially as described by Smith et al. (1996). ' Heterohybridoma culture supernatant containing huMabs was used after heat inactivation. None of the huMabs tested could neutralize a rabies virus strain CVS-BHK. Table 3: Survivorship of Swiss albino mice subjected to mouse neutralization test to demonstrate the ability of human monoclonal antibodies to neutralize various fixed and street rabies viruses in vivo S.No huMab" Virus SRV 108 SRV 141 SRV 142 SRV 129 1 R17D6 100% 100% 100% 100% 2 R14B3 ND* ND ND 100% 3 R16C9 100% 100% 100% 100% 4 R14D6 100% 100% 100% 100% 5 R18G9 100% 100% 100% 100% 6 R16F7 100% 100% 100% 100% 7 R17G9 100% 100% 100% 100% 8 R16E5 100% 100% 100% 100% * Not done * Heat inactivated heterohybridoma culture supernatant containing RVhuMabs was used for neutralization reaction. ^ Female Swiss albino mice (3-4 weeks old) were intracranialy inoculated with 30 ^1 of (50 MICLD50/3O nO either rabies virus infected culture fluid or brain homogenates from naturally infected rabid stray dogs. The inoculated mice were observed daily for symptoms typical of rabies for 21 days. The results are expressed as percentage of mice that survived after 21 days of observation. SEQ ID NO: 1 -Light Chain (669 nts) ATGCCCATGGACTCCTATGTGCTGACTCAGCCACCCTCGATGTCAGCGG CCCCAGGACAGACGGCCAGCATTACCTGTGGGATCAACAACAATGTCA TTAAAAGTGTGCACTGGTACCGGCAAAAGTCAGGCCCTGCGGTGGTCG TCTATGATGGTGGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGC CTCCGACTCTGCGAACACGGCCACCCTAAGCATCAGCAGGGTCGAGGC CGGGGATGAGGCCGACTATTATTGTCAGGTGTGGGATAGCAGTAGTGA GGATTTTTGGGTGTTCGGCGGAGGGACCCAGCTCACCGTTTTAGGTTTG ATCCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTG AGGAGCTCCAAGCCAACAAGGCCACACTAGTGTGTCTGATCAGTGACT TCTACCCGGGAGCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCG TCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAAC AAGTACGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAG TCCCACAGAAGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTG GAGAAGACAGTGGCCCCTACAGAATGTTCAGCGGCCGCCCAT SEQ ID NO: 2-Heavy Chain (1378 nts) ATGCCCATGGCAGGTGCAGCTGCAGGAGTCTGGGGGAAACCTGGTGCA GCCGGGGGGGTCCCTGAGACTCTCCTGTGAAGCCTCTGGATTCACCTTC GGAAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTG GAGTGGGTCGCAGCTATTAGTGGCAGTGGTCTTCACACATACTACGCG GACGCTGTGAAGGGCCGGTTCAGCATCTCCAGAGACAACTCCAAGAAC ACACTGTATTTGCAAATGAACAGCCTGAGAGCCGGGGACACGGCCATT TATTACTGTGCGAAGGATAAGGGCATAGTAGTGGCTACCATCTTCTTCT CCTGGGGCCAGGGCACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGG GCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGG CACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTG ACCGTGCCCTCCAGCAGCTTGAGCACCCAGACCTACATCTGCAACGTG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAA ATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTC CTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCC TCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGA GCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGC ACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGA ATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCC CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCAC AGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGG TCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGT GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCAC CGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGT GATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCT GTCTCCGGGTAAATGTGCGGCCGCCCAT SEQ ID NO: 3 Amino acid sequence of light chain MPMDSYVLTQPPSMSAAPGQTASITCGINNNVIKSVHWYRQKSGPAVVVY DGGDRPSGIPERFSASDSANTATLSISRVEAGDEADYYCQVWDSSSEDFWV FGGGTQLTVLGLIQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTV AWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV THEGSTVEKTVAPTECSAAAH SEQ ID NO: 4 Amino acid sequence of heavy chain CPWQVQLQESGGNLVQPGGSLRLSCEASGFTFGSYAMSWVRQAPGKGLE WVAAISGSGLHTYYADAVKGRFSISRDNSKNTLYLQMNSLRAGDTAIYYC AKDKGIVVATIFFSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLST QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KCAAAH SEQ ID NO: 5 Nucleotide sequence of CDRs of variable light chain GCCATGGCGTCCTATGTGCTGACTCAGCCACCCTCGATGTCAGCGGCCCCAGGACAGACG GCCAGCATTACCTGTGGGATCAACAACAATGTCATTAAAAGTGTGCACTGGTACCGGCAA AAGTCAGGCCAGGCCCCTGCGGTGGTCGTCTATGATGGTGGCGACCGGCCCTCAGGGATC CCTGAGCGATTCTCTGCCTCCGACTCTGCGAACACGGCCACCCTAAGCATCAGCAGGGTC GAGGCCGGGGATGAGGCCGACTATTATTGTCAGGTGTGGGATAGCAGTAGTGAGGATTTT TGGGTGTTCGGCGGAGGGACCCAGCTCACCGTTTTAGGT SEQ ID NO: 6 Nucleotide sequence of CDRs of variable heavy chain CAGGTGCAGCTGCAGGAGTCTGGGGGAAACCTGGTGCAGCCGGGGGGGTCCCTGAGACTC TCCTGTGAAGCCTCTGGATTCACCTTCGGAAGCTATGCCATGAGCTGGGTCCGCCAGGCT CCAGGGAAGGGGCTGGAGTGGGTCGCAGCTATTAGTGGCAGTGGTCTTCACACATACTAC GCGGACGCTGTGAAGGGCCGGTTCAGCATCTCCAGAGACAACTCCAAGAACACACTGTAT TTGCAAATGAACAGCCTGAGAGCCGGGGACACGGCCATTTATTACTGTGCGAAGGATAAG GGCATAGTAGTGGCTACCATCTTCTTCTCCTGGGGCCAGGGCACCCTGGTCACCGTCTCC TCAGAATTCCAA SEQ ID NO: 7 Deduced amino acid sequence of CDRs of variable light chain CDRs of VL underlined MASYVLTQPPSMSAAPGQTASITCGINNNVIKSVHWYRQKSGQAPAVWYDGGDRPSGIP ERFSASDSANTATLSISRVBAGDEADYYCQVWDSSSEDFVA^FGGGTQLTVL SEQ ID NO: 8 Deduced amino acid sequence of CDRs of variable heavy chain CDRs of VH underlined QVQLQESGGNLVQPGGSLRLSCEASGFTFGSYAMSWVRQAPGKGLEWVAAISGSGLHTYY ADAVKGRFSIS RDNSKNTLYLQMNSLRAGDTAIYYCAKDKGIWATIFFSWGQGTLVTVS REFERENCES • R J Cote, D M Morrissey, Generation of human monoclonal antibodies reactive with cellular antigens.Proc Natl Acad Sci USA. 1983 Apr; 80(7):2026-30. • Chin, J., Sohn, Y., Lee, S.H., Park, Y.L and Choi, M.J. (2003). Production of neutralizing human monoclonal antibody directed to tetanus toxin in CHO cell. Biologicals 31: 45-53. • Crawford, D.H (1985). Production of human monoclonal antibodies using Epstein-Barr virus. In E.G. Engleman, S.K. Foung, J. Larrick, A. Raubitschek. (Eds.), Human hybridomas and Monoclonal antibodies. Plenum Press, New York, USA. • Dorfman, N., Dietzschold, B., Kajiyama, W., Fu, Z.F., Koprowski, H. and Notkins, A.L. (1994). Development of human monoclonal antibodies to rabies. Hybridoma 13: 397-402. • Enssle, K., Kurrle, R., Kohler, R., Muller, H., Kanzy, E.J., Hilfenhaus, J. and Seller, F.R. (1994). A rabies-specific human monoclonal antibody that protects mice against lethal rabies. Hybridoma 10: 547-556. • Funaro, A., Horenstein, A.L., Ghisolfi, G., Bussolati, B., Bartorelli, A. and Bussolati, G. (1999). Identification of a 220-kDa membrane tumor-associated antigen by human anti-UK114 monoclonal antibodies selected from the immunoglobulin repertoire of a cancer patient. Experimental Cell Research 247: 441-450. • Green, L. (1999). Antibody engineering via genetic engineering of the mouse: Xenomouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. Journal of Immunological Methods 231: 11-23. • Hoogenboom, H.R. (2002). Overview of antibody phage-display technology and its applications. Methods in Molecular Biology 178: 1-37. • Ko, K., Wei, X., Crooks, P.A. and Koprowski, H. (2004). Elimination of alkaloids from plant-derived human monoclonal antibody. Journal of Immunological Methods 286: 79-85. Rando, R.F. and Notkins, A.L. (1994). Production of human monoclonal antibodies against rabies virus. Current Topics in Microbiology and Immunology 187: 195-205. Shay, J.W. (1985). Human hybridomas and monoclonal antibodies: the biology of cell fusion. In E.G. Engleman, S.K. Foung, J. Larrick, A. Raubitschek (Eds.), Plenum Press, New York, USA. Smith, J.S., Yager, P.A. and Baer, G.M. (1996). A rapid fluorescent focus inhibition test (RFFIT) for determining rabies virus-neutralizing antibody. In F.X. Meslin, M.M. Kaplan, and H. Koprowski (eds.) Laboratory techniques in rabies, 4* edn. Chapter 15, pp. 181-192, World Health Organization, Geneva, Switzerland. We Claim: 1. A fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence haying at least 95% identity with the nucleotide sequence as set forth in SEQ ID NO: 2. 2. A fully human monoclonal antibody against rabies comprising a heavy chain polypeptide encoded by a polynucleotide sequence having nucleotide sequence as set forth in SEQ ID NO: 1 and a light chain polypeptide encoded by a polynucleotide sequence having the nucleotide sequence as set forth in SEQ ID NO: 2. 3. The fully human monoclonal antibody as claimed in claim 2, wherein amino acid sequence of said heavy chain polypeptide is as set forth in SEQ ID NO: 3 and amino acid sequence of said light chain polypeptide is as set forth in SEQ ID NO: 4. 4. The fully human monoclonal antibody as claimed in claim 2, wherein said heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7. 5. The fully human monoclonal antibody as claimed in claim 2, wherein said heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 8 encoded by the nucleotide sequence as set forth in SEQ ID NO: 6 and a light chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 7 encoded by the nucleotide sequence as set forth in SEQ ID NO: 5. 6. A pharmaceutical composition for passive immunization of a subject against rabies, wherein said composition comprising the monoclonal antibody as claimed in any of the proceeding claims. 7. A process of detecting rabies virus antigen in a sample, said process comprising: contacting at least a portion of said sample with a fully human monoclonal antibody as claimed in claim 1 or claim 2 and determining the presence or absence of binding of said antibody to said antigen by conventional methods. 8. A kit for detection of rabies virus antigen in a sample, said kit comprising the human monoclonal antibodies as claimed in any of the proceeding claims and an assay manual to determine the reaction of said antigen with said antibody. 9. A process for producing the fully human monoclonal antibodies as claimed in any of the proceeding claims, wherein said process comprises: a. obtaining plurality of B peripheral lymphocyte from human vaccinated with Pasteur virus (PV) strain of rabies virus; b. stimulating said lymphocytes with a miotogen to obtain stimulated lymphocytes; c. fusing said stimulated lymphocytes with plurality of human-mouse myeloma to obtain stable heterohybridoma; and d. isolating said monoclonal antibodies from said heterohybridoma 10. The process as claimed in claim 9, wherein the mitogens is selected from a group consisting of phytohaemagglutinin (PHA), concanavalin A (conA), lipopolysaccharide (LPS) and pokeweed mitogen (PWM), preferably pokeweed mitogens (PWM).

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