Inactivation of the α C protein antigen gene, bca, by a novel shuttle/suicide vector results in attenuation of virulence and immunity in group B Streptococcus

J Li, DL Kasper, FM Ausubel… - Proceedings of the …, 1997 - National Acad Sciences
J Li, DL Kasper, FM Ausubel, B Rosner, JL Michel
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
The α C protein of group B Streptococcus (GBS) is a major surface-associated antigen.
Although its role in the biology and virulence of GBS has not been defined, it is opsonic and
capable of eliciting protective immunity. The α C protein is widely distributed among clinical
isolates and is a potential protein carrier and antigen in conjugate vaccines to prevent GBS
infections. The structural gene for the α C protein, bca, has been cloned and sequenced.
The protein encoded by bca is related to a class of surface-associated proteins of Gram …
The α C protein of group B Streptococcus (GBS) is a major surface-associated antigen. Although its role in the biology and virulence of GBS has not been defined, it is opsonic and capable of eliciting protective immunity. The α C protein is widely distributed among clinical isolates and is a potential protein carrier and antigen in conjugate vaccines to prevent GBS infections. The structural gene for the α C protein, bca, has been cloned and sequenced. The protein encoded by bca is related to a class of surface-associated proteins of Gram-positive cocci involved in virulence and immunity. To investigate the potential roles of the α C protein, bca null mutants were generated in which the bca gene was replaced with a kanamycin resistance cassette via homologous recombination using a novel shuttle/suicide vector. Studies of lethality in neonatal mice showed that the virulence of the bca null mutants was attenuated 5- to 7-fold when compared with the isogenic wild-type strain A909. Significant differences in mortality occurred in the first 24 h, suggesting that the role of the α antigen is important in the initial stages of the infection. In contrast to A909, bca mutants were no longer killed by polymorphonuclear leukocytes in the presence of α-specific antibodies in an in vitro opsonophagocytic assay. In contrast to previous studies, α antigen expression does not appear to play a role in resistance to opsonophagocytosis in the absence of α-specific antibodies. In addition, antibodies to the α C protein did not passively protect neonatal mice from lethal challenge with bca mutants, suggesting that these epitopes are uniquely present within the α antigen as expressed from the bca gene. Therefore, the α C protein is important in the pathogenesis of GBS infection and is a target for protective immunity in the development of GBS vaccines.
National Acad Sciences