RESUMEN
Safe recombinant vaccines, based on a small number of antigenic proteins, are emerging as the most attractive, cost-effective solution against infectious diseases. In the present work, we confirmed previous data from our laboratory showing that whole viable bacterial cell treatment with proteases followed by the identification of released peptides by mass spectrometry is the method of choice for the rapid and reliable identification of vaccine candidates in Gram-positive bacteria. When applied to the Group B Streptococcus COH1 strain, 43 surface-associated proteins were identified, including all the protective antigens described in the literature as well as a new protective antigen, the cell wall-anchored protein SAN_1485 belonging to the serine-rich repeat protein family. This strategy overcomes the difficulties so far encountered in the identification of novel vaccine candidates and speeds up the entire vaccine discovery process by reducing the number of recombinant proteins to be tested in the animal model.
Asunto(s)
Antígenos Bacterianos , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae , Vacunas Sintéticas , Secuencia de Aminoácidos , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Femenino , Datos de Secuencia Molecular , Proteoma/análisis , Streptococcus agalactiae/inmunología , Streptococcus agalactiae/patogenicidadRESUMEN
Pili are essential virulence factors in many Gram-negative bacteria; however, they have not been described in most important Gram-positive pathogens. While screening the sequence of multiple genomes of Group B Streptococcus, we identified protective antigens that formed high molecular weight polymers. Immunogold electron microscopy revealed that the structures have a pilus-like form. These large structures have gone unrecognized in decades of studies of Group B Streptococcus.
Asunto(s)
Antígenos de Superficie/análisis , Fimbrias Bacterianas/ultraestructura , Genoma Bacteriano , Streptococcus agalactiae/genética , Streptococcus agalactiae/ultraestructura , Animales , Antígenos Bacterianos/análisis , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Fimbrias Bacterianas/inmunología , Fimbrias Bacterianas/fisiología , Inmunohistoquímica , Ratones , Microscopía Inmunoelectrónica , Operón , Infecciones Estreptocócicas/inmunología , Streptococcus agalactiae/inmunología , Streptococcus agalactiae/patogenicidad , VirulenciaRESUMEN
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.