Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen

Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a major cause of life-threatening infections in newborns. To develop a broadly protective vaccine, we analyzed the genome sequences of eight GBS isolates and cloned and tested 312 surface proteins as vaccines. Four proteins elicited protection in mice, and their combination proved highly protective against a large panel of strains, including all circulating serotypes. Protection also correlated with antigen accessibility on the bacterial surface and with the induction of opsonophagocytic antibodies. Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens.

[1]  R. Rappuoli,et al.  Genome Analysis Reveals Pili in Group B Streptococcus , 2005, Science.

[2]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[3]  A. Schuchat,et al.  Perinatal infections due to group B streptococci. , 2004, Obstetrics and gynecology.

[4]  Oscar E. Gaggiotti,et al.  Ecology, genetics, and evolution of metapopulations , 2004 .

[5]  J. Troendle,et al.  Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen. , 2004, The Journal of infectious diseases.

[6]  D. Kasper,et al.  Glycoconjugate vaccines to prevent group B streptococcal infections , 2003, Expert opinion on biological therapy.

[7]  Philippe Glaser,et al.  Multilocus Sequence Typing System for Group B Streptococcus , 2003, Journal of Clinical Microbiology.

[8]  Ian T. Paulsen,et al.  Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Olmsted,et al.  Antibody against Surface-Bound C5a Peptidase Is Opsonic and Initiates Macrophage Killing of Group B Streptococci , 2001, Infection and Immunity.

[10]  L. Paoletti Potency of clinical group B streptococcal conjugate vaccines. , 2001, Vaccine.

[11]  I. Charlebois,et al.  Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity , 2000, Infection and Immunity.

[12]  J. Venter,et al.  Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. , 2000, Science.

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

[14]  A. Schuchat Group B streptococcus , 1999, The Lancet.

[15]  Peter Kareiva,et al.  Conservation biology: for the coming decade. , 1998 .

[16]  P. Turchin Quantitative analysis of movement : measuring and modeling population redistribution in animals and plants , 1998 .

[17]  P. Model,et al.  Cell wall sorting signals in surface proteins of gram‐positive bacteria. , 1993, The EMBO journal.

[18]  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.

[19]  D. Kasper,et al.  Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein , 1992, Infection and immunity.

[20]  D. Kasper,et al.  Immunization of Pregnant Women with a Polysaccharide Vaccine of Group B Streptococcus , 1988 .

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

[22]  S. Goldhor Ecology , 1964, The Yale Journal of Biology and Medicine.