Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity

ABSTRACT A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 434 amino acid residues, with a calculated pI of 6.84 and molecular mass of 45.5 kDa. Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.

[1]  G. Lindahl,et al.  Group B Streptococcal Surface Proteins as Targets for Protective Antibodies: Identification of Two Novel Proteins in Strains of Serotype V , 1999, Infection and Immunity.

[2]  S. Melville,et al.  Cloning, Sequence, and Transcriptional Regulation of the Operon Encoding a Putative N -Acetylmannosamine-6-Phosphate Epimerase (nanE) and Sialic Acid Lyase (nanA) inClostridium perfringens , 1999, Journal of bacteriology.

[3]  N. Cadieux,et al.  Antigenic and Molecular Conservation of the Gonococcal NspA Protein , 1999, Infection and Immunity.

[4]  D. Kasper,et al.  Alpha C Protein as a Carrier for Type III Capsular Polysaccharide and as a Protective Protein in Group B Streptococcal Vaccines , 1999, Infection and Immunity.

[5]  D. Kasper,et al.  Serotypes VI and VIII predominate among group B streptococci isolated from pregnant Japanese women. , 1999, The Journal of infectious diseases.

[6]  G. Lindahl,et al.  Protection against experimental infection with group B streptococcus by immunization with a bivalent protein vaccine. , 1999, Vaccine.

[7]  A. Schuchat.  Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms , 1998, Clinical Microbiology Reviews.

[8]  A. Schuchat,et al.  Serotype distribution of invasive group B streptococcal isolates in Maryland: implications for vaccine formulation. Maryland Emerging Infections Program. , 1998, The Journal of infectious diseases.

[9]  P. Azimi,et al.  Capsular polysaccharide types of group B streptococcal isolates from neonates with early-onset systemic infection. , 1997, The Journal of infectious diseases.

[10]  W. Simpson,et al.  Cloning and sequence analysis of zooA, a Streptococcus zooepidemicus gene encoding a bacteriocin-like inhibitory substance having a domain structure similar to that of lysostaphin. , 1997, Gene.

[11]  N. Cadieux,et al.  Highly Conserved Neisseria meningitidis Surface Protein Confers Protection against Experimental Infection , 1997, The Journal of experimental medicine.

[12]  L. Madoff,et al.  Characterization of two distinct opsonic and protective epitopes within the alpha C protein of the group B Streptococcus , 1997, Infection and immunity.

[13]  L. Wright,et al.  Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. , 1997, Pediatrics.

[14]  D. Kasper,et al.  Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. , 1996, The Journal of clinical investigation.

[15]  G. Lindahl,et al.  Experimental vaccination against group B streptococcus, an encapsulated bacterium, with highly purified preparations of cell surface proteins Rib and alpha , 1996, Infection and immunity.

[16]  G. Lindahl,et al.  Identification of a Family of Streptococcal Surface Proteins with Extremely Repetitive Structure* , 1996, The Journal of Biological Chemistry.

[17]  K. Timmis,et al.  Identification of an immunoglobulin A binding motif located in the beta-antigen of the c protein complex of group B streptococci , 1996, Infection and immunity.

[18]  E. Swiatlo,et al.  PspA, a protection-eliciting pneumococcal protein: immunogenicity of isolated native PspA in mice. , 1996, Vaccine.

[19]  A. Schuchat,et al.  Prevention of perinatal group B streptococcal disease : a public health perspective , 1996 .

[20]  D. Schendel,et al.  Prevalence of selected developmental disabilities in children 3-10 years of age: the Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1991. , 1996, MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries.

[21]  A. Schuchat,et al.  Invasive group B streptococcal disease: the emergence of serotype V. , 1996, The Journal of infectious diseases.

[22]  D. Kasper,et al.  Immunogenicity and protective activity in animals of a type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. , 1995, The Journal of infectious diseases.

[23]  O. Schneewind,et al.  Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in Gram‐positive bacteria , 1994, Molecular microbiology.

[24]  M. Cunningham,et al.  Cloning and sequence analysis of a gene encoding a 67-kilodalton myosin-cross-reactive antigen of Streptococcus pyogenes reveals its similarity with class II major histocompatibility antigens , 1994, Infection and immunity.

[25]  D. Kasper,et al.  Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine , 1993, Infection and immunity.

[26]  G. Lindahl,et al.  Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections , 1993, The Journal of experimental medicine.

[27]  F. Ausubel,et al.  Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Oliver,et al.  Differentiation of Streptococcus uberis from Streptococcus parauberis by polymerase chain reaction and restriction fragment length polymorphism analysis of 16S ribosomal DNA , 1991, Journal of clinical microbiology.

[29]  G. Dunny,et al.  Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci , 1991 .

[30]  D. Kasper,et al.  Phenotypic diversity in the alpha C protein of group B streptococci , 1991, Infection and immunity.

[31]  E. Fikrig,et al.  Protection of mice against the Lyme disease agent by immunizing with recombinant OspA , 1990, Science.

[32]  D. Kasper,et al.  Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. , 1989, The New England journal of medicine.

[33]  P. Ferrieri,et al.  Molecular species of R-protein antigens produced by clinical isolates of group B streptococci , 1989, Journal of clinical microbiology.

[34]  R. Watson,et al.  A Bacteriophage λ cI857 Cassette Controls λ PL Expression Vectors at Physiologic Temperatures , 1987, Bio/Technology.

[35]  D. Kasper,et al.  Isolation of a C (Ibc) protein from group B Streptococcus which elicits mouse protective antibody. , 1986, Microbial pathogenesis.

[36]  Dwight R. Johnson,et al.  Group B streptococcal Ibc protein antigen: distribution of two determinants in wild-type strains of common serotypes , 1984, Journal of clinical microbiology.

[37]  D. Kasper,et al.  Antibody to group B Streptococcus type III in human sera measured by a mouse protection test , 1981, Infection and immunity.

[38]  L. Bevanger,et al.  Complete And Incomplete Ibc Protein Fraction in Group B Streptococci , 1979, Acta pathologica et microbiologica Scandinavica. Section B, Microbiology.

[39]  D. Kasper,et al.  Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. , 1976, The New England journal of medicine.

[40]  M. Mccarty,et al.  Multiple mouse-protective antibodies directed against group B streptococci. Special reference to antibodies effective against protein antigens , 1975, The Journal of experimental medicine.

[41]  R. G. Eagon,et al.  Type-Specific Antigens of Group B Type Ic Streptococci , 1971, Infection and immunity.

[42]  L. Bevanger,et al.  An apparently new strain-variable Streptococcus agalactiae protein. , 1997, Advances in experimental medicine and biology.

[43]  P. Ferrieri,et al.  Surface protein expression in group B streptococcal invasive isolates. , 1997, Advances in experimental medicine and biology.