Title of Invention	"A RECOMBINANT POLYPEPTIDE FOR INDUCING AN IMMUNE RESPONSE SPECIFIC FOR GROUP B STREPTOCOCCUS"
Abstract	Group B Streptococcus (GBS) proteins and polynucleotides encoding them are disclosed, said proteins are antigenic and therefore useful vaccine components for the prophylaxis or therapy of streptococcus infection in animals. Also disclosed are recombinant methods of producing the protein antigens as well as diagnostic assays for detecting streptococcus bacterial infection.

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GROUP B STREPTOCOCCUS ANTIGENS FIELD OF THE INVENTION The presant invention is related to antigens, more particularly protein antigens of group B Streptococcus (GBS) bacterial pathogen which are useful as vaccine conponents for therapy and/or prophylaxis. BACKGROUND OF THE INVENTION Streptococcus are gram (+) bacteria that are differcatiated by group specific carbohydrate antigens A through O found on their cell surface. Streptococcus groups are further distinguished by type-specific capsular polysaccharide antigens. Several serotypes have been identified for the Group B Streptococcus (GBS) : Ia, Ib, II, III, IV, V, VI, VII and VIII. GBS also contains antigenic proteins known as "C-proteins" (alpha, beta, gamma and delta), some of which have been cloned. Although GBS is a common component of the normal htsnan vaginal and colonie flora this pathogen has long been recognized as a major căuşe of neonatal sepsis and meningitis, late-onset meningitis in infants, postpartum endometritis as well as mastitis in dairy herds. Expectant mothers exposed to GBS are at risk of postpartum infect ion and may transfer the infection to their baby as the chila passes through the birth canal. Although the organism is sensitive to antibiotics, the high attack rate and rapid onset of sepsis in neonates and meningitis in infants results in high morbidity and mortality. wo 99/42588 To fine a vaccine that will protect individuals from G3S infection, researches nave curned co the type-specific antigens. Unfortunately these polysaccharides have proven te be poorly immunogenic in humans, and are rescricced to the particular serotype from which the polysaccharide originates. Further, capsular polysaccharide elicit a T cell independent response i.e. no IgG production. Consequently capsuiar polysaccharide antigens are unsuitable as a vaccine component for protection against GBS infection. Others have focused on the C-protein beta antigen which demonstrated imnamogenic properties in mice and rabbit models. This procein was found to be unsuitable as a human vaccine because of its undesirable property of interacting with high affinity and in a non-immunogenic manner with the Fc region of huma* igA. The C-protein alpha antigen is rare in type III serotypes of GBS which is the serotype rcsponsible for aost GBS mediated conditions and is therefore of little use as a vaccine component. Therefore there remains an unmet need for GBS antigens that may be used as vaccine components for the prophylaxis and/or therapy of OBS infection. SUMMARY OF THE HWENTION According to one aspect, the presant invention provides an isolated polynucleotide cncoding a polypeptide having at least 70V identity to a second polypeptide comprising a sequence selected from the group consisting of: SEQ ID NO: 2, SBQ ID NO: 3; SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SBQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID N0:12, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID N0:16, SEQ ID N0:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID N0:20, SEQ ID N0:21, SEQ ID N0:23, SEQ ID N0:24, SEQ ID NO:25, SEQ ID N0:26, SEQ ID N0:28, SEQ ID N0:29, SEQ ID N0:30, SEQ ID N0:31, SSQ ID N0:33, SEQ ID N0:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID N0:36, SEQ ID N0:39, SEQ ID NO: 40, SEQ ID NO:41 and SEQ ID NO:44 or fragraents, analoga or derivacives thereof. In ocher aspects, there is provided vectors comprising polynucleotides of the invention operably linked to an expression control region, as well as nost cells transfected with said vectors and methods of producing polypeptides comprising culturing said host cells under conditions suitable for expression. In yet another aspect, there is provided novei polypeptides encoded by polynucleotides of the invention. BRIEF DESCRIPTION OF THE DRAWINGS Figure la is the DNA sequence of clone l (SEQ ID NO :1) with corresponding amino acid sequences for open reading frames; figure Ib is the amino acid sequence SEQ ID NO: 2; figure Ic is the amino acid sequence SEQ ID NO: 3; figure Id is the amino acid sequence SEQ ID NO: 4 ,- figure le is the amino acid sequence SEQ ID NO: 5; figure If is the amino acid sequence SEQ ID NO: 6; Figure 2a is the DNA sequence of clone 2 (SEQ ID NO :7) with corresponding amino acid sequences for open reading frames; figure 2b is the amino acid sequence SEQ ID NO; 8; figure 2c is the amino acid sequence SEQ ID NO: 9; figure 2d is the amino acid sequence SEQ ID NO:10; figure 2e is the amino acid sequence SEQ ID NO:11; figure 2f is the amino acid sequence SEQ ID HO: 12; Figure 3a is the DNA sequence of clone 3 (SEQ ID NO :13) with corre.sponding amino acid sequences for open reading f rame s,- figure 3b is che amino acid sequence SEQ ID NO:14; figure 3c is che amino acid sequence SEQ ID NO:15; figure 3c is che amino acid sequence SEQ ID NO:16; figure 3e is che amino acid sequence SEQ ID NO:17; figure 3f is Che amino acid sequence SEQ ID NO:18; figure 3g is che amino acid sequence SEQ ID NO:19; figure 3h is che amino acid sequence SEQ ID NO:20; figure 3i is Che amino acid sequence SEQ ID N0:21; Figure 4a is Che DNA sequence of clone 4 (SEQ ID NO :22) with corresponding amino acid sequences for open reading frames; figure 4b is the amino acid sequence SEQ ID NO:23; figure 4c is the amino acid sequence SEQ ID NO:24; figure 4d is the amino acid sequence SEQ ID NO:25; figure 4e is the amino acid sequence SEQ ID NO:26; Figure Sa is the DNA sequence of clone 5 (SEQ ID NO :27) with corresponding amino acid sequences for open reading frames; figure 5b is the amino acid sequence SEQ ID NO:28; figure Se is the amino acid sequence SEQ ID NO:29; figure 5d is the amino acid sequence SEQ ID NO:30; figure 5e is the amino acid sequence SEQ ID NO:31; Figure 6a is the DNA sequence of clone 6 (SEQ ID NO :32) ; figure 6b is the amino acid sequence SEQ ID NO:33; figure 6c is the amino acid sequence SEQ ID NO:34; figure 6d is the amino acid sequence SEQ ID NO:35; figure 6e is the amino acid sequence SEQ ID NO:36; Figure 7 a is the DNA sequence of clone 7 (SEQ ID NO :37); figure 7b is the amino acid sequence SEQ ID NO:38; figura 7c is the amino acid sequence SEQ ID NO:39; figure 7d is the amino acid sequence SEQ ID NO:40; figure 7e is the amino acid sequence SEQ ID N0:4i; Figure 8 is the DNA sequence of a part of clone 7 including a signal sequence (SEQ ID NO :42); Figure 9 is the DNA sequence of a part of clone 7 without a signal sequence (SEQ ID NO :43) ; Figure 9a is the amino acid sequence (SEQ ID N0:44); Figure 10 represents the distribution of anti-G3S ELISA titers in sera from CD-1 mice immunized with recombinant GBS protein corresponding to the SEQ ID N0:39. DETAILED 3ESCRIPTION OF THE INVENTION The preseac invention relates co novei antigenic polypeptides of group B streptococcus (GBS) characcerized by the amino acid sequence selected from the group ccnsisting of : SEQ ID NO; 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID N0:10, SEQ ID NOsll, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID N0:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID N0:23, SEQ ID N0:24, SEQ ID NO:25, SEQ ID NO:2S, SEQ ID NO:28, SEQ ID NO:29, SEQ ID N0:30, SEQ ID NO.-31, SEQ ID NO:33, SEQ ID NO.-34, SEQ ID N0:35, SEQ ID NO:36, SEQ ID NO:38, SEQ ID N0:39, SEQ ID N0:40, SEQ ID NO:41 and SEQ ID NO:44 or fragments, analogs or derivacives thereof. A preferred embodiment of the invention includes SSQ ID NO :39 and SEQ ID NO:44. A further preferred embodiment of the invention is SEQ ID NO :39. A further preferred embodiment of the invention is SEQ ID NO :44. As used hcrein, "fragments", "derivatives" or "analogs" of the polypeptides of the invention include those polypeptides in which one or more of the amino acid residues are substituted with a conserved or non-conserved amino acid residue (preferably conserved) and which may be natural or unnatural. The terms «fragments», «derivatives» or «analogues» of polypeptides of the present invention also include polypeptides which are modified by addition, deletion, substitucion of amino acids provided t hat the polypeptides recain the capacity to induce an immune response. 3y che term «conserved amino"acid» is meant a subsnicution of ane or more amino acids for another in which che anugenic determinant (including its secondary scructure and hydropathic nature) of a given ancigen is completely or partially conserved in spiţe of the substitution. For exair.ple, one or more amino acid residues within the seguance can be substituted by another amino acid of a similar polarity, which acts as a funcţional equivalent, resulting in a silent alteration. Substitutes for an amino acid within the sequence may be selected from other members of the class to which the amino acid belongs. For example, the nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine. The polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. Preferably, derivatives and analogs of polypeptides of the invention will nave about 70% identity with those sequences illustrated in the figures or fragments thereof. That is, 70% of the residues are the same. More preferably polypeptides will have greater than 95% homology. In another preferred embodiment, derivatives and analogs of polypeptides of the invention will have fewer than about 20 amino acid residue substitutions, modifications or deletions and more preferably less than 10. Preferred substitutions are those known in the art as conserved i.e. the substituted residues share physical or chemical properties such as hydrophobicity, size, charge or funcţional groups. Furchermore, in those situations where amino acid regions are found to be polymorphic, ic may .toe desirable to vary one «, or more particular amino acids" to more effectively mimic the different epitopes of the different GBS strains. Also included are polypeptides which foave fused thereto other corapounds which alter the polypeptides biological or pharmacological properties i.e. polyccltylene glycol (PEG) to increase half-life; leader or secretory amino acid sequences for ease of purification; preprp- and pro- sequences; and (poly)saccharides. Moreover, the polypeptides of the present invention can be modified by terminal -NHa acylation (cg. by acetylation, or thioglycolic acid araidation, terminal carbosy amidation, e.g. with atnmonia or methylamine) to provide stability, increased hydrophobicity for linking or binding to a support or other molecule. Also contemplated are hetero and homo polypeptide multimers of the polypeptide fragments, analogues and derivatives. These polymeric forms include, for example, one or more polypeptides that have been cross-linted with cross-linkers such as avidin/biotin, gluteraldehyde or dimethyl-superimidate. Such polymeric forms also include polypeptides containing two or more tandem or inverted contiguous sequences, produced from miticistronic mRNAs generated by recombinant DNA tecnnologrjr. Preferably, a fragment, analog or derivative of a polypeptide of the invention will coaprise at least one antigenic region i.e. at least one epitope. In order to achieve the formation of antigenic polymers (i.e. synthetic multimers), polypeptides may be utilized having bishaloacetyl groups, nitroarylhalides, or the liJce, where che reagencs being specific for thio groups. Therefore, the link between two mercapto groups of che different peptides may be a single bond or may be composeci v of a linking group of ac. leasc'cwo, cypically ac leasc four, and noc more chan 16, but usually noc more chan abouC 14 carbon acoms. In a parcicular embodimenc, polypepcide fragmencs, analogs and derivacives of che invencion do noc concain a mechionine (Mec) scarcing residue. Preferably, polypepcides will noc incorporaCe a leader or secrecory sequence (signal sequence). The signal porcion of a polypepcide of che invencion may be decermined according co escablished molecular biological Cechniques. In general, Che polypepcide of interese may be isolaced from a GBS culcure and subsequencly sesquenced Co deCermine the inicial residue of the macure protein and therefor che sequence of che mature polypepcide. According Co anocher aspecC, chere is provided vaccine composicions comprising one or more GBS polypeptides of Che invencion in admixture wich a pharmaceutically acceptable carrier diluenc or adjuvanc. Suitable adjuvancs include oils i.e. Freund's complece or incomplete adjuvant; salCs i.e. AlK(SO,),, AlNa(SO,),, A1NH, (SO,),, Al (OH),, A1PO4, silica, kaolin; saponin derivacive; carbon polynucleotides i.e. poly IC and poly AU and also detoxified cholera toxin (CTB)and E.coli heat labile toxin for induction of mucosal immunity. Preferred adjuvants include QuiLA™, Alhydrogel™ and Adjuphos™. Vaccines of the învention may be administered parenterally by injection, rapid infusion, nasopharyngeal absorption, dermoabsorption, or bucal or oral. Vaccine compositions of the invention are used for the creatment or prophylaxis of s creptococcus infection and/or v diseases and symptoms mediated by screpcococcus infection, ir. parcicular group A s crep tococcus (pyocrenes) , group B screpcococcus (GBS or agalactiae), dysgalactiae, uberis, nocardia as well as Staphylococcus aureus. General information âbout Streptococcus is ayailable in Manual of Clinical Microbiology by P.R.Murray et al. (1995, 6th Edition, ASM Press, 'Washington, D.C.). More parcicularly group B screpcococcus, agralactiae. In a particular embodiment vaccines are administered to those individuals at risk of GBS infection such as pregnant women and infants for sepsis, meningitis and pneumonia as well as inanunocompromised individuals such as those with diabetes, liver disease or cancer. Vaccines may also nave veterinary applications such as for the treatment of mastitis in cattle which is mediated by the above mentioned bacteria as well as E.coli. The vaccine of the present invention can also be used for - the manufacture of a medicament used for the treatment or prophylaxis of screp tococcus infection and/or diseases and symptoms mediated by screpcococcus infection, in particular group A screpcococcus (pyogenes), group B screpcococcus (GBS or agralactiae}, dysgralaceiae, uberis, nocardia as well as Scaphylococcus aureus. More particularly group B screpcococcus, agralacCiae. Vaccine compositions are preferably in unit dosage form of about 0.001 to 100 ug/kg (antigen/body weight) and more preferably O.Ol to 10 ug/kg and most preferably 0.1 to l Ug/kg l to 3 times with an interval of about l to 12 weeks intervals between immunizations, and more preferably l to 6 weeks. According to another aspect, chere is provided polynucleocides encoding polypeptides of group B streptococcus (GBSJ characcerized by che amino acid sequence selected from che group consisting of: SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID N0:ll, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:23, SEQ ID N0:24, SEQ ID N0:25, SEQ ID NO:26, SEQ ID N0:28, SEQ ID N0:29, SEQ ID NO-.30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID N0:34, SEQ ID N0:35, SEQ ID NO:36, SEQ ID NO:38, SEQ ID N0:39, SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:44 or fragments, analogs or derivatives thereof. ' Preferred polynucleocides are chose illuscraced in figures la (SEQ ID NO: 1), 2a (SEQ ID NO: 7), 3a (SEQ ID NO: 13), 4a (SEQ ID NO: 22), Sa. (SEQ ID NO: 27), 6a (SEQ ID NO: 32), 7a (SEQ ID NO: 37), 8 (SEQ ID NO : 42) and 9 (SEQ ID NO : 43) which correspond co che open reading frames, encoding polypepcides of the invencion. Preferred polynucleocides are chose illuscraced in figures la (SEQ ID NO: 1), 2a (SEQ ID NO: 7), 3a (SEQ ID NO: 13), 4a (SEQ ID NO: 22), 5a (SEQ ID NO: 27), 6a (SEQ ID NO: 32), 7a (SEQ ID NO: 37), 8 (SEQ ID NO : 42) and 9 (SEQ ID NO : 43) and fragmenCs, analogues and derivaCives chereof. More preferred polynucleocides of Che invencion are Chose illuscrated in Figures 7 (SEQ ID NO : 37) , B (SEQ ID NO : 42) and 9(SEQ ID NO : 43). Mosc preferred polynucleocides of Che invencion are chose illuscraced in Figures 8 (SEQ ID NO : 42) and 9 (SEQ ID NO : 43) . It will be appreciated that the polynucleotide sequences illustrated in the figures may be alcered with degenerate codons yet still encode the polypeptides of the invention. Due to the degeneracy of nucleotide coding seguences, other polynucleotide sequeaces which encode for substantially the same polypeptides of the present invention may be used in the practice of the present invention. These include but are not limited to nucleotide sequences which are altered by the substitution of different codons that encode the same amino acid residue within the sequence, thus producing a silent change. Accordingly the present invention further provides polynucleotides which hybridize to the polynucleotide sequences herein above described (or the complement sequences thereof) having 50% and preferably at least 70% identity between sequences. More preferably polynucleotides are hybridizable undcr stringent condiţiona i.e. having at least 95% identity and most preferably more than 97% identity. By capable of hybridizing under stringent conditions is meant annealing of a nucleic acid molecule to at least a region of a second nucleic acid sequence (whether as cDNA, mRNA, or genomic DNA) or to its complementary ştrand under standard conditions, e.9. high temperature and/or low salt content, which tend to disfavor hybridization of noncomplementary nucleotide sequences. A suitable protocol is described in Maniatis T. et al., Molecular cloning : A Laboratory Manual, Cold Springs Harbor Laboratory, 1982, which is herein incorporated by reference. In a further aspect, polynucleotides encoding polypeptides of the invention, or fragments, analogs or derivatives thereof, may be used in a DNA immunizacion method. That is, they can be incorporated into a veccor which is replicafale and expressible upon injection thereby producing the antigenic polypepticie in vivo. For example polynucleotides may be incorporated into a plasmid vector under the control of the CMV promoter which is funcţional in eukaryotic cells. Preferably the vector is injected intramuscularly. According to another aspect, there is provided a process for producing polypeptides of the invention by recombinant techniques by expressing a polynucleocide encoding said polypeptide in a nost cell and recovering the expressed polypeptide product. Alternaţively, the polypeptides can be produced according to established synchetic chemical techniques i.e. solution phase or solid phase synthesis of oligopeptides which are ligated to produce the full polypeptide (block ligation). For recombinant production, nost cells are transfected with vectors which encode the polypeptide, and then cultured in a nutrient media raodified as appropriate for activating promoters, selecting transformants or amplifying the genes. Suitable vectors are those that are viable and replicable in the chosen host and include chromosomal, non-chromosomal and synthetic DNA sequences e.g. bacterial plasmids, phage DNA, baculovirus, yeast plasmids, vectors derived from combinations of plasmids and phage DNA. The polypeptide sequence may be incorporated in the vector at the appropriate site using restriction enzymes such that it is operably linked to an expression control region comprising a. promoter, ribosome binding site (consensus region or Shine-Dalgarno sequence), and optionally an operator (control element). One can select individual components of the expression control region that are appropriate for a given host and vector according to established molecular biology principles (Sambrook et al, Molecular Cloning: A Laboratory Manual, 2nd ed. , Cold SpringvHarbor, N.Y-, 1989 incorporated herein by reference). Suitable promoters include but are not limited to LTR or SV40 proraoter, E. coli lac, tac or trp promoters and the phage larabda PL promoter. Vectors will prefarably incorporate an origin of repiication as well as selection markers i.e. aropicillin resistance gene. Suitable bacterial vectors include pET, pQE70, pQE60, pQE-9, pbs, pDIO phagescript, psiX174, pbluescript SX, pbsks, pNHSA, pNHlfia, pNHISA, pNH46A, ptrc99a, pKK223-3, pKK233-3, pDR540, pRITS and eukaryotic vectors pBlueBacIII. pWLNEO, pSV2CAT, pOG44, pXTl, pSG, pSVK3, pBPV, pMSG and pSVL. Host cells may be bacterial i.e. E.coli, flacillus subtilis, IStreptomyces; fungal i.e. Aspergrillus nigrer, Aspergrillus nidulins; yeast i.e. Saccharomyces or eukaryotic i.e. CHO, COS. Upon expression of the polypeptide in culture, cells are typically harvested by centrifugation then disrupted by physical or chemical means (if the expressed polypeptide is not secreted into the media) and the resulting crude extract retained to isolate the polypeptide of interest. Purification of the polypeptide from culture media or lysate may be achieved by established teehniques depending on the properties of the polypeptide i.e. using ammonium sulfate or ethanoi precipitation , acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, hydroxylapatite chromatography and lectin chromatography. Final purification may be achieved using HPLC. The polypeptide may be expressed with or without a leader or secretion sequence. In the former case the leader may be removed using post-translational processing (see US 4,431,739; 4,425,437; and 4,338,397 incorporated herein by reference) or be chemically removed subsequent to purifying the expressed polypeptide. v According to a further aspect, the GBS polypeptides of the invention raay be used in a diagnostic test for streptococcus infection in particular GBS infection. Several diagnostic methods are possible, for example detecting streptococcus organism in a biological sample, the following procedure may be followed: a) obtaining a biological sample f rom a patient; b) incubating an antibody or fragment thereof reactive with a GBS polypeptide of the invention with the biological sample to form a mixture; and c) detecting specifically bound antibody or bound fragment in the mixture which 'indicates the presence of streptococcus. Alternatively, a method for the detection of antibody specific to a streptococcus antigen in a biological sample containing or suspected of containing said antibody may be performed as follows: a) isolating a biological sample from a patient; b) incubating one or more GBS polypeptides of the invention or fragments thereof with the biological sample to form a mixture; and c) detecting specifically bound antigen or bound fragment in the mixture which indicates the presence of antibody specific to streptococcus. One of skill in the art will recognize that this diagnostic test may take several forms, including an immunological test such as an enzyme-linked immunosorbent assay (ELISA), a radioimmunoassay or a latex agglutination assay, essentially to determine whether antibodies specific for the protein are present in. an organism. The DNA sequences encoding polypeptides of the invention may also be used to design DNA ptobes for use in detecting che presence of strepcococcus in a biological sample suspecced of containing such bacteria- The detection mechod of this invencion comprises: a.) isolating the biological sample f rom a patient; b) incubating one or more DNA probes having a DNA sequence encoding a polypeptide of the invention or fragments thereof with the biological sample to form a mixture; and c) detecting specifically bound DNA probe in the mixture which indicates the presence of streptococcus bacteria. The DNA probes of this invention may also be used for detecting circulating streptococcus i.e. GBS nucleic acids in a sample, for example using a polymerase chain reaction, as a method of diagnosing streptococcus infections. The probe may be synthesized using convenţional techniques and may be immobilized on a solid phase, or may be labeled with a detectable labei. A preferred DNA probe for this application is an oligomer having a sequence complementary to at least about 6 contiguous nucleotides of the GBS polypeptides of the invention. Another diagnostic «ethod for the detection of streptococcus in a patient comprises: a) labe ling an antibody reactive with a polypeptide of the invention or fragment thereof with a detectable labei; b) administering the labeled antibody or labeled fragment to the patient; and c) detecting specifically bound labeled antibody or labeled fragment in the patient which indicates the presence of streptococcus. A further aspect of the invention is the use of the GBS polypepcides of the invenCion as immunogens for the procîuction of specific ancibodies for the diagnosis and in particular the treatmenc of screptococcus infection. Suitable ancibodies may be determined using appropriate screening tnethods, for exatrtple by measuring the ability of a particular antibody to passively protect against streptococcus infection in. a test model. One example of an aniraal model is the mouse model described in the examples herein. The antibody may be a whole antibody or an antigen-binding fragment thereof and may in general belong to any iramunoglobulin class. The antibody or fragment may be of animal origin, specifically of mammalian origin and more specifically of «urine, rât or human origin. It may be a natural antibody or a fragment thereof, or if desired, a recombinam: antibody or antibody fragment. The term recombinant antibody or antibody fragment means antibody or antibody fragment which were produced using molecular biology techniques. The antibody or antibody fragments may be polyclonal, or preferably monoclonal. It may be specific for a number of epitopes associated with the GBS polypeptides but is preferably specific' for one. EXAMPLE l Murine model of lethal Group B Streptococcus (GBS) infection The mouse model of GBS infection is described in detail in Lancefield et al (J Exp Hed 142:165-179,1975). GBS străin C388/90 (Clinical isolate obtained in 1990 f r om the cephalorachidian fluid of a patient suffering from meningitis, Children's Hospital of Eastern Ontario, Ottawa, Canada) and NCS246 (National Center for Streptococcus, Provincial Laboratory of Public Health for Northern Alberta, Edmonton, Canada) were respectively serotyped as type Ia/c and type II/R. To increase their virulence, che GBS strains C388/90 (serotype Ia/c) and NCS 246 (serotype II/R) were serially passaged through mice as described previously (Lancefield et al. J Exp Med 142:165-179, 19*75) . Briefly, che increase of virulence was monitored using intraperitoneal inoculations of serial dilutions of a subculture in Todd-Hewitc broth obtained from either the blood or spleen of infected mice. After the last passage, infected blood samples were used to inoculate Todd-Hewitt broth. After an incubation of 2 hours at 37eC with 7% C02, glycerol at a final concentration of 10% (v/v) was added to the culture. The culture was then aliquoted and stored at -80° C for use in GBS challenge experimenta. The number of cfu of GBS present in these frozen samples was determined. The bacterial concentration necessary to kill 100% (LD100) of the 18 weeks old mice were determined to be 3.5X10*and 1.1X10* respectively for GBS străin C388/90 and NCS246, which corresponded to a significant increase in virulence for both strains. Indeed, the LD100 recorded before the passages for these two strains was higher than 10* cfu. In a bacterial challenge, a freshly thawed aliquot of a virulent GBS străin was adjusted to the appropriate bacterial concentration using Todd-Hewitt broth and îmi was injected intraperitoneally to each female CD-l mouse. The mice used for the passive protection experiments were 6 to 8 weeks old, while the ones used for the active protection experimenta were approximately 18 weeks old at the time of the challenge. AII inocula were verified by colony counts. Animala were observed for any sign of infection four times daily for the first 48 h after challenge and then daily for the next 12 days. At the end of that period, blood samples were obtained from the survivors and frozen at -20°C. The spleen obtained from each mouse that survived the challenge was cultured in order to identify any remaining GBS. EXAMPLE 2 Immunization and protection in mice with formalciehyde killed whole GBS cells Formaldehyde killed GBS whole cells were prepared according co the procedures described in Lancefield ec al (J Exp Med 142:165-179,1975). Briefly, an overnight culture on sheep blooc agar plates (Quelab Laboratories, Montreal, Canada) of a GBS scrain was washed twice in PBS buffer (phosphate buffered-saline, pH7.2), adjasted to approximately 3X101 cfu/»L and incubaced overnigfec in PBS containing 0.3% (v/v) f ormaldehyde. The killed GBS suspension was washed with PBS and fcepc frozen at -80°C. Female CD-1 mice, 6 to 8 weeks old (Charles River, St-Constant, QuSbec, Canada), were injected subcutaneously three times at two weeks interval with 0.1 ral of forraaldehyde killed cells of GBS străin C388/90 (~6X107 GBS), or O.l ml of PBS for the control group. On the day before the iromunization, Alhydrogel1** (Superfos Biosector, Frederikssund, Denmark) at a final concentration of 0.14 mg or 0.21 mg of Al, was added co these preparations and incubated overnight at 4°C with agitation. Serum samples were obtained from each mouse before the beginning of the immunization protocol and two weeks after the last injection. The sera were frozen at -20°C. Eight mice in each control group injected with PBS and the group immunized with formaldehyde killed whole cells GBS străin C388/90 (Ia/c) were challenged with 1.5X104 cfu of GBS scrain C388/90 (la/c) one week after the third injection. AII mice immunized with the formaldehyde killed GBS whole cells survived the homologous challenge while, within S days after the challenge, only 4 out of the 8 mice injecced with PBS survived from the infect ion. In order to increase the mortality rate in the control groups, the suspends hâd to be adjusted according to the age of the mice at the time of the bacterial challenge In suosequenc challenge experimenta, wnen mice were older tv-ar 15 weeks, the bacterial inoculum was increased to concentrations between 3.0X105 and 2 5X1C' cfuTable l immunization of CD1 mice wich formaldehyde killed whole cells of GBS and subsequent hcrnclogous cnallenge fscrain C388/90 (Ia/ci ar.d hecerologous cKallenge {străin NCS246 (II/R)3 . (Table Removed) 1 alhydfOflif' at a final concentration of 0.14 mg or 0.21mg of Al was used; 2 approximely 6X107cfu; intraperitoneal chaitenge with 1 mL Todd-Hewitt culture medium containing GBS C388/90 (la/c) pension adjusted to 1.5X104 cfu; 4 intraperitoneal cha«enge with 1 mL Todd-Hewitt culture medium containing GBS C388/90 (la/c) suspension adjusted to 2.1X10* cfu: s not done: * intrapertoneal chattenge with 1 mL Todd-Hewitt culture medium containing GBS NCS246 (II/R) suspension adjustedto 1.2X105 cfu. In another experiment, one group of 12 mice corresponding to a control group was injected with PBS, while a second group of 12 mice was immunized with formaldehyde killed whole cells of GBS străin C388/90 (Ia/c) . Six mice from each of these two groups were challenged with 2.1X10* cfu of the GBS străin C388/90 (Ia/c) (Table I). As the first challenge experiment, all mice immunized with the GBS străin C388/90 (Ia/c) survived the homologous challenge. Only two out of the 6 mice injected with PBS survived the infeetion. SUBSTITUTE SHEETmill P *ttThe remaining 6 mice in both groups were then used one week later to verify whether- this ancigenic preparation could confer cross proteccion against străin NCS246 (ÎI/R) whicn produce a serologically distinct capsule. None of che mice infected with this second G3S străin survived the infection. The later result suggested that most of the proiective immune response induced by formaldehyde killed szrair. C386/90 is directed against the capsular polysaccharide and that it could be restricted to strains of chac particular serotype. These results clearly indicated chat this particular model of infection can be efficiently used to study the protection conferred by vaccination. EXAMPLE 3 Iranunization of rabbit with formaldehyde killed whole GBS cel îs and passive protection in mice A New Zealand rabbit (2.5 kg, Charles River, St-Constant, Quâbec, Canada) was immunized with formaldehyde killed cells of GBS străin C388/90 (la/c) to obtain hyperimmune serum. This rabbit was injected subcutaneously three times at three weeks interval with approximately 1.5X10* cfu of formaldehyde killed whole cells of GBS străin C388/90 (la/c). Freund's complete adjuvant (Gibco BRL Life Technologies, Grand Island, New York) was used as the adjuvant for the first immunization, while Freund's incomplete adjuvant (Gibco BRL) was used for the following two injections. Serum samples were obtained before the beginning of the immunization protocol and two weeks after the last injection. The sera were frozen at -20°C. The ability of this particular rabbit hyperimmune serum to passively protect mice against a lethal infection with GBS 22 SUBSTnrtlTP SMPPTffttll P was also evaluated. Jntraperitoneal injection of mine with either 15 or 25 nL of hyperinanune rabbic serum 18 hours before the challenge protectsd. 4 cuc of 5 mice {80%1 against the infect ion. Comparat iveiy, survival rateş lower a-harţ 20% were recorded for mice in the contrei group injected with FBS or seruri obtained from a rabbit immunized with meningococcal outer membrane preparation. This resmlt clearly indicates that the iwiunization of another aanimal species with killed GBS cells can induce the production of antibodies that can passively protect mice. This reagent will also be used to characterize clones. Table 2 Passive protection of CD-1 mice conferred toy rabbit serum obtained after immunization with formaldehyde killed group B whole streptooocci (străin C388/90 (Ia/c)) antigenic preparation (Table Removed) 1 Freund's complete adjuvant vas used for first immunization, and Freund's incomplete adjuvant for the following two injections; 1 intraperitoneal challenge with l ral Todd-Hewitt culture medium containing GBS C388/90 (Ia/c) suspension adjjusted to 2X104 cfu. EXAMPLE 4 Recombinanc production of His.Tag-GBS fusion protein v The coding region of a GBS gene was amplified by PCR (DNA Thermal Cycler GeneAmp PCR system 2400 Perkin Elmer. Sân Jose, CA) f rom the genomic DNA of GBS străin C388/SO (Ia/c) using the oligos that contained base extensions for the addition of the restriction sites BglII (AGATCT) and Hindlll (AAGCTT), respectively. The PCR product was purified from agarose gel using a Qiaex II gel extraction kit from Qiagen (Chatsworth, CA), digested with the restriction enzymes BglII and Hindlll (Pharmacia Canada Inc Baie d'Urfe, Canada), and extracted with phenol:chloroforo before ethanol precipitation. The pET-32b(+) vector (Novagen, Madison, WI) containing the thioredoxin-His.Tag sequence «as digested with the restriction enzymes BglII and Hindlll, extracted with phenol: chlorof orm, and then ethanol precipitated. The BglII-HindIII genomic DNA fragment was ligated to the Bglll-HindlII pET-32b(+) vector to create the coding sequence for thioredoxin-His.Tag-GBS fusion protein whose gene was under control of the T7 promoter. The ligated products were transformed into E. coli străin XLI Blue MRF' (A(mcrA) 183A (jncrCB-JîsdSMR-,mrr)173 endAl supE44 thi-1 recftl gyrA96 relAl lac IF'proAB lad'ZAMlSTnlO (Tetr)]c) (Stratagene, La Jolla, CA) according to the method of Simanis (Hanahan, D. DNA Cloning, 1985, D.M. Glover (ed.), pp. 109-135). The recombinant pET plasmid was purified using a Qiagen kit (Qiagen, Chatsworth, CA) and the nucleotide sequence of the DNA inaert was verif ied by DNA sequencing (Taq Dye Deoxy Terminator Cycle Sequencing kit, ABI, Poster City, CA) . The recombinant pET plasmid was transformed by electroporation (Gene Pulser II apparatus, BIO-RAD Labs, Mississauga, Canada) into E. coli străin AD494 (DE3) (Aara'leu7697 AlacX74 AphoA PvuII phoR AraalF3 F1 {lac*(Iaci») pro] trxB::Kan (DE3)) (Novagen, Madison, WI). In this străin of E. coli, the T7 promocer controlling expression of the fusion protein, is specifically recognized by the T7 RNA \ * polymerase (present on the XDE3 prophage) whose gene is under the control of the lac promoter which is inducible by isopropyl-jJ-D-thio-galactopyranoside (IPTG) . The transformant AD494(DE3)/rpET was grown at 37°C with agitation at 250 rpm in LB broth (peptone 10g/L( Yeast extract Sg/L, NaCl lOg/L) containing lOOng of ampicillin {Sigma-Aldrich Canada Ltd., Oakville, Canada) per mL until the AJUD reached a value of 0.6. In order to induce the production of the thioredoxin-His.Tag-GBS fusion protein, the cel îs were incubated for 2 additional hours in the presence of IPTG at a final concentration of ImM. The bacterial cells were harvested by centrifugation. The recorabinant fusion protein produced by AD494(DE3)/rpET32 upon IPTG induction for 2h was partially obtained as insoluble inclusion bodies which were purified from endpgenous E. coli proteins by the isolation of insoluble aggregates (Gerlach, G.F. et al 1992, Infect. Immun. 60:892). Induced cells from a 500 mL culture were resuspended in 20 mL of 25% sucrose-SOmM Tris-HCl buffer (pHB.O) and frozen at -70°C. Lysis of cells in thawed suspension was achieved by the addition of 5mL of a solutiom of lysozyae (lOrag/mL) in 250mM Tris-HCl buffer (pH8.0) followed by an incubation of 10 to 15 min bn ice, and the addition of iSOmL of detergent mix (S parts of 20mM Tris-HCl buffer tpH7.4]-300mM NaCl-2% deoxycholic acid-2% Nonidet P-40 and 4 parts of lOOmM Tris-HCl buffer (pH8]-SOmM EDTA-2V Triton X-100) followed by 5 min incubation on ice. Upon sonication, protein aggregates were harvested by centrifugation for 30 min at 35,000 X g and a sample of the soluble cellular fraction was kept. The aggregated proteins were solub'ilized in 6M guanidine hydrochloride. The presence of the fusion protein in both the soluble and insoluble fractions was shown by Western Blot analysis using the serura of a mouse injected\wich formaldehyde Jcilled cells of GBS străin C388/90 (la/c) that survived a bacterial challenge with the corresponding G3S străin. The purification of the fusion protein frora the soluble fraction of IPTG-induced AD494(DE3)/rpET was done by affinity chromatography based on the properties of the His.Tag sequence (6 consecutive histidine residues) to bind to divalent cations (Ni**) immobilized on the His.Bind metal chelation resin (Novagen, Madison, WI). The purification method used are those described in the pET system Manual, 6th Edition (Novagen, Madison, WI) . Briefly, the pelleted cells obtained from a lOOroL cu l tur e induced with IPTG was resuspendcd in 4mL of Binding buffer (5mM imidazole-SOOmM NaCl-20mM Tris-HCl pH7.9), sonicated, and spun at 39,000 X g for 20 min to reraove debris. The supernatant was filtered (0.45nm pore size membrane) and deposited on a column of His.Bind resin equilibrated in Binding buffer. The colunm was then washed with 10 column volumes of Binding buffer followed by 6 column volumes of Wash buffer (20mM imidazole-SOOraM NaCl-20mM Tris-HCl pH7.9). The thioredoxin-His.Tag-GBS fusion protein was eluted with Elute buffer (IM imidazolc-SOOraM NaCl-20mM Tris-HCl pH7.9). The removal of the salt and itnidazole from the s ample was'done by dialysis against 3X1 liter PBS at 4°C. The quantities of fusion protein obtained from either the soluble or insoluble cytoplasmic fractions of E. coli were estimated by Cooraassie staining of a sodium dodecyl sulfat» (SDS)-polyacrylaraide gel with serial dilutions of these proteina and a bovine serum albumin standard (Pierce Chemical Co. Rockford, 111.). EXAMPLE 5 Recombinant prociuction of GBS protein under control of lambda PL promocer The DNA coding region of a GBS.protein was inserted downstream of the promoter XPL into the translation vector pURV22. This plasmid was derived from p629 (George et al. 1987, Bio/Technology 5:600) from which the coding regim for a portion of the herpes simplex virus type I (HSV-l) glycoprotein (gD-1) was removed and the ampicillin resistance gene replaced by a kanamycin cassette obtained from the plasmid vector pUC4K (Pharmacia Biotech Canada Inc., Baie D'Urfe, Canada). The vector contained a cassette of the bacteriophage X cI857 temperature sensitive repressor gene from which the funcţional P, promoter hâd been deleted. The inactivation of the cI857 repressor by temperature increase from the ranges of 30-37ac to 37-42°C resultcd in the induction of the gene under the control of X PL. The translation of the gene was controlled by the ribosome binding eite cro followed downstream by a BglII restriction site (AGATCT) and the ATG: ACTAAGGAGGTTAGATCTATG. Restriction enzymes and T4 DNA ligase were used accordisag to suppliers (Pharmacia Biotech Canada Inc., Baie D'Urfe, Canada; and New England Biolabs Ltd., Mississauga, Canada). Agarose gel electrophoresis of DNA fragments was perforaned as described by Sambrook et al. ( Molecular clonino ; A laboratorv Manual. 1989, Cold Spring Harbor Laboratory Press, H. Y) . Chromosomal DNA of the GBS bacteria was prepared according to procedures described in Jayarao «t al (J. Clin. Microbiol., 1991, 29:2774). DNA amplification reactions by polymerase chain reaction (PCR) were made wsing DNA Thermal Cycler GeneAmp PCR system 2400 (Perkin Elraer. Sân Jose, CA) . Plasmids used for DNA sequencing were purified using plasmid kits from Qiagen (Chatsworth, C&>. DNA fragmente were purif ied from agarose gels using Qiaex II gel extraction kits f rom Qiagen (Chatsworth, CA) . Plasmid transformations were carried out by the method described by Hanahar. (DNA Cloninc. Glover \(ed.). pp, 109-135, 1985). The sequencing of genomic DNA inserts in plasmids was done using synthetic oligonucleotides which were synthesized by oligonucleotide synthesizer model 394 (the Perkin-Elmer Corp., Applied Biosystems Div. (ABI), Poster City, CA). The sequencing reactions were carried out by PCR using the Taq Dye Deoxy Terminator Cycle Sequencing kit (ABI, Foster City, CA) and DNA electrophoresis was performed on automated DNA sequencer 373A (ABI, Foster City, CA) . The assembly of the DNA sequence was performed using the program Sequencer 3.O (Gene Codes Corporation, Ann Arbor, MI) . Analysis of the DNA sequences and their predicted polypeptides was performed with the program Gene Works version 2.45 (Intelligenetics, Inc., Mountain View CA). The coding region of the GBS gene was amplified by PCR f r om GBS străin C388/90 (la/c) genomic DNA using oligos that contained base extensions for the addition of restriction sites BglII (AGATCT) and Xbal(TCTAGA), respectively. The PCR product was purified from agarose gel using a Qiaex II gel axtraction kit from Qiagen (Chatsworth, CA), digested with the restriction enzymes BglII and Xbal, and extracted with phenol:chloroform before ethanoi precipitation. The pURV22 vector was digested with the restriction enzymes BglII and Xbal, extracted with phenol:chloroform, and ethanol precipitated. The BglII-Xbal genomic DNA fragment was ligated to the BglII-Xbal pURV22 vector in which the GBS gene was under the control of the XPL promoter. The ligated productş were transformed into E. coli străin XLI Blue MRF1 (A (mcrA)183A(jJîcrCB-lisdSMR-mrr)173 endAl supE44 thi-1 recAl gyrA96 relAl lacCF1 proAB laclqZAM15 TnlO (Tetr) ]c) (Stratagene, La Joi la CA) according to the methods described in Hanahah, supra. Transformants harboring plasmids with the insert were identified by analysis of lysed cells subroitted to electrophoresis on agarose gel (Sambrook e t al, surora). The recombinam: pURV22 piasmi-d. .was purified using a Qiagen kit (Qiagen, Chatsworth, CA) and the nucleotide sequence of the DNA inserc was verified by DNA sequencing. The transformant XLI Blue MRF'/rpURV22 was grown at 34°C wich agitation at 250 rpm in LB broth containing SOug of kanamycin per raL unt i l the A,00 reached a value of 0.6. in order to induce the production of the fusion protein, the cells were incubated for 4 additional hours at 39°C. The bacterial cells were harvested by centrifugation , resuspended in saraple buffer, boiied for 10 min and kept at -20«C. EXAMPLE 6 Subcloning GBS protein gene in CMV plasmid pCMV-GH The DNA coding region of a GBS protein was inserted in phase downstreara of the human growth hortnone (hGH) gene which was under the transcriptional control of the cytomegalovirus (CMV) proaoter in the plasmid vector pCMV-GH (Tang et al, Nature, 1992, 35€il52). The CMV prorooter ie non funcţional in E. coli cells but active upon administration of the plasmid in eukaryotic cells. The vector also incorporated the ampicillin re*dstance gene. The coding region of the gene was amplified by PCR from genomic DNA of GBS străin C388/90 (la/c) using the oligos that contained ba*e extensions for the addition of the restriction siţes BglII (AGATCT) and HindIII (AAGCTT). The PCR product was purified from agarose gel using a Qiaex II gel extraction kit from Qiagen (Chatsworth, CA), digested with the restriction enzymes BglII and HindIII, and extracted with phenol:chloroform before ethanoi precipitation. The pCMV-GH vector (Laboratory of Dr. Stephen A. Johnscon, Department of Biochemistry, The University of Texas, Dallas, Texas) containing the human growth hormone to create fusion proteins was digegted with the restriction enzymes BamHI and HindIII, extracted with phenol:chloroform, and ethanol precipitated. The 1.3-kb BglII-HindIII genomic DNA fragment was ligated to the BamHI -HindIII pCMV-GH vector to create the hGK-GBS fusion protein under the control of the CMV promoter. The ligated products were transformed into E. coli străin DH5ot$80 lacZ AM15 end&l recAl hsdRl? (rK~TC*) supE44 thi-lX' gyrA96 relAl A(lac2YA-argrF)U169] (Gibco BRL, Gaithersburg, MD) according to the methods described by Hanahan, supra. Transformants harboring plasmids with the insert were identified by analysis of lyaed cells submitted to electrophoresis on agarose gel (Sarabrook, J. et al , suara) . The recombinant pCMV plasmid was purified using a Qiagen kit (Qiagen, Chatsworth, CA) and the nucleotide sequence of the DNA insert was verified by DNA sequencing. EXAMPLE 7 Imraunological activity of GBS protein to GBS challenge Four groups of 12 female CD-1 aice (Charles River, St-Constant, Quebec, Canada) of 6 to 8 weeks were injected subcutaneously three times at three week intervals with O.lmL of the following antigenic preparations: formaldehyde killed cells of GBS străin C388/90 (~€X107 cfu), 20(ig of thioredoxin-His. Tag-GBS fusion protein obtained f rom the insoluble (inclusion bodies) or 20(ig of the fusion protein, affinity purified (nickel coluom), frora the soluble cytoplasmic fraction in £.coli. or 20ftg of af f inity purif ied (nickel column) thioredoxin-His.Tag control polypeptide. 20^lg of QuilA™ (Cedarlane Laboratories Ltd, Hornby, Canada) was added co each antigenic preparacion as the adjuvant. Serum samples were obtained from each mouse before immunization (PB) and on dayâ 20 .(TB1) , 41 (TB2) and 54 (TB3) during the immunization protocols. Sera were frozen at -20°C. An increase of the ELISA titers was recorded after each injection of the fusion protein indicating a good primary response and a boost of the specific humoral insaune response after each of the second and third administration. At the end of the immunization period, the means of reciprocal ELISA titers was 456,145 for the group immunized with 20|ig of fusion protein obtained from inclusion bodies compărea to 290,133 for the group of mice immunized with the protein. from soluble fraction in E.coli. The latter result suggests that the protein obtained from inclusion bodies could be more immunogenic than the solubie protein. Analysis of mice sera in ELISA using the affinity purified thioredoxin-His.Tag to coat plates showed that negligible antibody titers are made against the thioredoxin-His.Tag portion of the fusion protein. The reactivity of the sera from nice injected with the recombinant fusion protein was also tcsted by ELISA against formaldehyde killed whole cells of GBS străin C388/90. The antibodies induced by itraaunization with recombinant fusion protein also recognized their specific epitopes on GBS cells indicating that their conformaţie» is close enough to the native streptococcal protein to induce cross-reactive antibodies. To verify whether the immune response induced by immunization could protect against GBS infecţie», mice were challenged with 3.5X10* cfu of GBS strains C338/SO(Ia/ci and 1.2X10* cfu of străin NCS246UI/R) the results of which are illustrated in tables 3 and 4 respectively. Mice immunized with control thioredoxin-His.Tag peptide were not protected against challenge with either GBS străin while those inununized wich formaldehyde killed C388/90 whole cells only provided protection against homologous challenge. The thioredoxin-His.Tag-GBS fusion protein of the invention protected mice from challenge with both GBS strains. Blood and spleen culture of these caice did not reveal the presence of any GBS. Table 3 Survival from GBS străin C388/90 (Ia/c) challenge1 (Table Removed) 1 intraperitoneal administration with l ml Todd-Hewitt culture medium adjusted to 3.5X10* cfu; 1 20jig administered; posterior legs paralyzed in surviving mouse; GBS detected in blood and spleen; 1 6X107 cfu administered; 4 20fig administered. Table 3 Survival from GBS străin C388/90 (Ia/c) challenge1 (Table Removed) 1 intraperitoneal administration with l ml Todd-Hewitt cuiture mediura adjusted to 3.5X10* cfu; 3 20\ig administered; posterior legs paralyzed in surviving mouse; GBS detected in blood and spleen; 1 6X107 cfu administered; 4 20|ig administered.Table 4 Survival from C-BS străin NCS246 (II/R) challenge1 (Table Removed) 1 intraperitoneal administration with l ml Todd-Hewitt cultura medium containing GBS NCS246(II/R) suspension adjusted to 1.2X10* cfu. 2 20ng administered; 1 6X10' cfu administered; 4 one mouse died during immunization. EXAMPLE 8 Immunization with recombinant GBS protein confers protection against experimental GBS infection This example illustrates the protection of mice against fatal GBS infection by immunization with the recombinant protein corresponding to the SEQ ID NO:39. Groups of 10 female CD-1 mice (Charles River) were immunized subcutaneously three times at three-week intervals with 20 pg of recombinant protein purified from E. coli străin BLR (Novagen) harboring the recombinant pURV22 plasmid vector containing the GBS gene corresponding to SEQ ID NO:42 in presence of 20 pg of QuilA™ adjuvant (Cedarlane Laboratories Ltd, Hornby, Canada) or, as control, with QuilA™ adjuvant alone in PBS. Blood samples were collected f rom the orbital sinus on day l, 22 and 43 prior to each iramuni:ation and fourteen days -(day 57) following the third injection. One week later the mice were challenged with approximately IO4 to IO6 CFU of various virulent GBS strains„ Samples of the GBS challenge inoculum were plated on TSA/5* sheep blood agar plates to determine the CFU and to verify the challenge dose. Deaths were recorded for a period of 1« days and on day 14 post-challenge, the surviving raice were sacrificed and blood and spleen were tested for the presenoe of GBS organisras. The survival data are shown in table 5, Prechallenge sera were analyzed for the presence of antibodies reactive with GBS by standard immunoassays. El i*» and immunoblot analyses indicated that immunization with recombinant GBS protein produced in E. coli elicited antibodies reactive with both, recombinant and native GBS protein. Antibody responses to GBS are described in Exanple 9. Table 5. Ability of recorobinant GBS protein corresponding to SEQ ID NO: 39 to elicit protection against 8 diverse GBS challenge strains (Table Removed) Groups of 10 mice per group were used, the number of mice surviving to infection and the nanber of dead mice are indicated. The survival curves corresponding to recombinant GBS protein-imraunized animals were compared to the survival curves corresponding to mock-innnnized animals using the log-rank test for nonparametric analysis. 2 Comparison analysis to NCS915-F-i*nunized animals. 3 Animals were immunized with formaldehyde-killed GBS in presence of QuilA™ adjuvant. All hemocultures from surviving mice were negative at day 14 post-challenge. Spleen cultures fiora surviving mice were negative except for few mice from experiment MB-11. EXAMPLE 9 Vaccination with the recombînant GBS protein elicits an immune response to GBS v Groups of 10 female CD-1 mice were immunized subcutaneously with recombinant GBS protein corresponding to SEQ ID NO:39 as described in Example 8. In order to assess the antibody response to native GBS protein, sera from blood samples collected prior each immunization and fourteen days after the third iramunization were tested for antibody reactive with GBS cells by ELÎSA using plates coated with formaldehyde-killed GBS cells from type III străin NCS 954, type Ib străin ATCC12401, type V străin NCS 535 or type VI străin NCS 9842. The specificity of the raised antibodies for GBS protein was confirmed by Western blot analyses to GBS cell extracts and purified recombinant antigens. The results shown in Figure 10 clearly demonstrate that animals respond strongly to recombinant GBS protein used as imrounogens with median reciprocal antibody titers varying between 12000 and 128000, for sera collected after the third immunization, depending of the coating antigen. AII preimmune sera were negative when tested at a dilution of l :100. GBS-reactive antibodies were detectable in the sera of each animal after a single injection of recombinant GBS protein.Example 10 Antigenic conservation of the GBS protein of the present invention Monoclonal antibodies (MAbs) specific to the GBS protein of the present invention were used to demonstrate that this surface antigen is produced by all GBS and that it is also antigenically higMy conserved. A collection of 68 GBS isolates was used to evaluate the reactivity of the GBS-specific MAbs. These strains were obtained from the National Center for Streptococcus, Provincial Laboratory of Public Health for Northern Alberta, Canada; Centre Hospitalier Universitaire de Quebec, Pavilion CHUL, Quebec, Canada; American Type Cui tur e Collection, USA; Laboratoire de Sânte Publigue du Quebec, Canada; and Dept. of Infectious Disease, Children's Hospital and Medical Center, Seattle, USA. AII eight Mabs were tested against the following panel of strains: 6 isolates of serotype Ia or la/c, 3 isolates of serotype Ib, 4 isolates of serotype II, 14 isolates of serotype III, 2 isolates of serotype IV, 2 isolates of serotype V, 2 isolates of serotype VI, 2 isolates of serotype VII, l isolate of serotype VIII, 10 isolates that were not serotyped and 3 bovine 5. agalactiae strains. MAb 3A2 was also reacted with additional GBS: 9 isolates of serotype la/c and 10 isolates of serotype V. The strains were grown ovemight on blood agar plates at 37°C in an atmosphere of 5% CC>2. Cultures were stored at - 70°C in heart infusion broth with 20% (v/v) glycerol. To obtain the GBS protein-specific MAbs, mice were inununized three tines at three-week intervals with 20 jig of purified recombinant GBS protein.(SEQ ID NO :44) in the presence of 20% QuilA1* adjuvant. Hybridoma cell lines were generated by fusion of spleen cells recovered from inununized mice with the nonsecreting SP2/O myeloma cell line as described previously (Hamei, j. et al. 1987. J. Med. Microbiol. 23:163-170). Hybrid clone supernatants were tested for specific antibody production by ELISA using formaldehyde inactivated GBS and purified•recorobinant GBS protein (SEQ ID NO :39 or 44) as coating antigen, as previously describeo (Hamei, J. ec al. 1987. J. Med. Microbiol. 23:163-170). Specific hybrid were cloned by limiting dilutions, expaoâed, and frozen in liquid nitrogen. Production of recombinam GBS protein was presented in Examples 4 & 5. Purified recombinant GBS protein or formaldehyde inactivated GBS «ere resolved by electrophoresis by using the discontinuous buf fer system of Laemmli as recontmended by the manufactraer and then transfer onto nitrocellulose membrane for Westeans immunoblotting as described previously (Martin et al. 1992. Infect. Immun. €0:2718-2725). f Western immunoblotting experimenta clearly indicated tihat all eight MAbs recognized a protein bând that corresponded to the purif ied recombinant GBS protein (SEQ ID NO :39). These MAbs also reacted with a protein bând present in evcry GBS isolates tested so far. The reactivity of these GBS-specific MAbs are presented in Table 6. Each MAb reacted well with all 46 GBS. In addition, these MAbs also recognized the 3 S. «galactlae strains of bovine origia tthat were tested. MAb 3A2 also recognized nineteen GBS; 9 isolates of serotype la/c and 10 of serotype V. The otiber MAbs were not tested against these additional strains. These reaults denonstrated that the GBS protein (SEQ XB NO :3i) tos produced by all the 65 GBS and the three 3 S. agalactiae strains of bovine origin that were tested' so far. More iflportantly, these results clearly demonstrated that the epitopes recognized by these eight GBS-specific MAbs were widely distributed and conserved among GBS. These results also indicated that these epitopes were not restricted to serologically reiacea isolates since repreaentatives of all knovm GBS serotypes including the r disease causing groups V«re tested. In conclusion, Che data presenced in this example clearly aemonstraced that the GBS protein of the present invention îs produced by all GBS and that it is antigenically higily COnserireH 3 conserved.Table 6. Reactivity of eight GBS protein-specif ic MAbs with different S. aga ] .1 r-r. i a ^ ntrainn as evaluated by Western immunoblots. (Table Removed) 1 Nine additional strains of serotype Ia/c and 10 strains of serotype V were recognized by MAb 3A2. 2 These strains were not serotyped WE CLAIM 1. A recombinant polypeptide comprising an amino acid sequence having minimum 70% homology to the amino acid sequence selected from SEQ ID NO: 39 and SEQ ID NO: 44, or comprising a fragment of the amino acid sequence selected from SEQ ID NO: 39 and SEQ ID NO: 44, wherein the recombinant polypeptide or the fragment has the N-terminal Met or secretory amino acid sequence deleted and retains the capacity of inducing an immune response specific for group B streptococcus. 2. The recombinant polypeptide as claimed in claim 1, consisting of an amino acid sequence having minimum 95% homology to the amino acid sequence set forth in SEQ ID NO: 39. 3. The recombinant polypeptide as claimed in claim 1 consisting of an amino acid sequence having minimum 95% homology to the amino acid sequence set forth in SEQ ID NO: 44. 4. The recombinant polypeptide as claimed in claim 1 consisting of an amino acid sequence according to SEQ ID NO: 39. 5. The recombinant polypeptide as claimed in claim 1 consisting of an amino acid sequence according to SEQ ID NO: 44. 6. A transfected microbial host cell producing the recombinant polypeptide as claimed in claims 1-5. 7. The recombinant polypeptide as claimed in claims 1-5, in the form of a medicament for group B streptococcus.

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