Preventing Bacterial Infections with Pilus-Based Vaccines: the Group B Streptococcus Paradigm

Abstract

We recently described the presence of 3 pilus variants in the human pathogen group B streptococcus (GBS; also known as Streptococcus agalactiae), each encoded by a distinct pathogenicity island, as well as the ability of pilus components to elicit protection in mice against homologous challenge. To determine whether a vaccine containing a combination of proteins from the 3 pilus types could provide broad protection, we analyzed pili distribution and conservation in 289 clinical isolates. We found that pilus sequences in each island are conserved, all strains carried at least 1 of the 3 islands, and a combination of the 3 pilus components conferred protection against all tested GBS challenge strains. These data are the first to indicate that a vaccine exclusively constituted by pilus components can be effective in preventing infections caused by GBS, and they pave the way for the use of a similar approach against other pathogenic streptococci.

Sequence type 1 group B Streptococcus , an emerging cause of invasive disease in adults, evolves by small genetic changes

“…The genome was 2,092,071 bp with 2,061 predicted ORFs and contains genes predicted to encode alpha-like protein (Alp) 3 (Alp3) and pilus 1 and 2a (Fig. 1A) (21,22). Compared with GBS strains whose complete genomes are available from the National Center for Biotechnology Information (NCBI), strain SGBS001 was most similar to the serotype V Swedish cow mastitis strain 09mas018883 (also ST-1; Fig.…”

Structural vaccinology to thwart antigenic variation in microbial pathogens

“…All GBS isolates examined to date elaborate pili, long filamentous structures that protrude from the bacterial surface (5). Genome sequence information from many GBS isolates revealed three pilus islands, designated PI-1, -2a, and -2b (15). GBS isolates harbor one or two of the three islands, either PI-1 and -2a or PI-2a and -2b (15).…”

“…Genome sequence information from many GBS isolates revealed three pilus islands, designated PI-1, -2a, and -2b (15). GBS isolates harbor one or two of the three islands, either PI-1 and -2a or PI-2a and -2b (15). Each pilus island represents a cluster of three subunit genes that encode one major [backbone protein (BP)] and two minor pilins of which ancillary protein 1 (AP1) functions as the tip adhesin, whereas AP2 represents the base subunit for pilus attachment to the cell wall envelope (16).…”

“…Sortase enzymes catalyze pilus assembly and attachment to the cell wall envelope. With the exception of the backbone protein for PI-2a (BP2a), which elaborates at least six immunological variants, the ancillary and backbone proteins of GBS pili display sequence conservation (15). When used as subunit vaccines in preclinical trials with a neonatal mouse challenge model, BPs elicit higher levels of GBS disease protection than APs (15).…”

“…With the exception of the backbone protein for PI-2a (BP2a), which elaborates at least six immunological variants, the ancillary and backbone proteins of GBS pili display sequence conservation (15). When used as subunit vaccines in preclinical trials with a neonatal mouse challenge model, BPs elicit higher levels of GBS disease protection than APs (15). The protective antigen status of BPs is attributable to pilus structure: sortases form pili from single subunits of AP1 or AP2 but incorporate several hundred BP pilins (16).…”