Serial dilutions were plated for determination of CFU on CHROMagar StrepB plates

Serial dilutions were plated for determination of CFU on CHROMagar StrepB plates. Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease, and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12 and 14 days, respectively. We defined LO disease as >7 days of life in the perinatal model. We studied the impact of maternal immunization using a whole-cell GBS vaccine on the duration of intestinal colonization and progression to invasive disease after postnatal GBS exposure in offspring. Animals exhibit sustained GI colonization following both perinatal and postnatal exposure to GBS, with 21% and 27%, JLK 6 respectively, developing invasive disease. Intestinal colonization with GBS induces an endogenous IgG response within 20 days of exposure. Maternal vaccination with whole-cell GBS induces production of GBS-specific IgG JLK 6 in dams that is vertically transmitted to their offspring but does not decrease the duration of GBS intestinal colonization or reduce LO mortality following postnatal GBS exposure. Both perinatal and postnatal murine models of GBS acquisition closely recapitulate the human disease state, in which GBS colonizes the intestine and causes LO disease. We demonstrate both endogenous production of anti-GBS IgG in juvenile mice and vertical transfer of antibodies to offspring following maternal vaccination. These models serve as a platform to study critical host-pathogen interactions that JLK 6 mediate LO GBS disease. == INTRODUCTION == Streptococcus agalactiae(group BStreptococcus[GBS]) is a leading cause of infectious morbidity and mortality in infants. Maternal rectovaginal colonization serves as the major reservoir for GBS, and transmission to the newborn typically occurs in the perinatal or early postnatal period (1). The widespread implementation of intrapartum antibiotic prophylaxis of GBS-colonized mothers has drastically reduced the incidence of early-onset infection (occurring in the first week of life) (2). However, the incidence of late-onset (LO) infection (occurring at >7 days of life) remains unchanged, and it is now the most common manifestation of invasive GBS disease in infants according to recent surveillance studies (3). LO GBS disease has an overall case fatality rate of 2 to 7%, which is notably higher (22%) in very low-birth-weight infants (4). Despite its importance, there are no effective strategies to reduce the incidence of LO disease or to identify those infants who may be most at risk (5). Prior studies indicate that intestinal colonization with GBS is an important precursor to the development of LO disease (6,7). Approximately 50% of infants with LO disease are colonized at birth with the same GBS serotype as the mother (6), and 40% of infants who are Acta2 colonized with GBS at birth continued to have intestinal carriage at 12 weeks of life (7). The host-pathogen interactions that mediate sustained intestinal colonization or drive the progression to LO disease in the newborn are limited, due in part to a paucity of robust animal models. Susceptibility to early-onset (EO) GBS infection in the neonate is inversely correlated with the presence of GBS-specific capsular polysaccharide-specific antibodies in the mother (8). Here, we describe two murine models of LO GBS infection, demonstrating both perinatal and postnatal acquisition. We then explore the role of endogenous antibody and the role of specific immunization strategies on the kinetics of intestinal colonization JLK 6 and progression to LO GBS disease. == RESULTS == == Perinatal GBS transmission. == We intravaginally infected dams on JLK 6 pregnancy day 17 to study perinatal GBS transmission. Liveborn animals were assessed daily, and serial perianal swabs were collected. Perianal swabs demonstrated that 80% of GBS-exposed offspring were colonized with GBS at 11 and 18 days of life (Fig. 1A). More than half of liveborn animals survived beyond the first week of life (Fig. 1B). Of those surviving pups, 21% died, which we attributed to invasive GBS disease despite initial asymptomatic carriage (Fig. 1C). The remaining animals eventually cleared GBS colonization by 4 weeks of age. == FIG 1. == A model of perinatal GBS transmission and LO infection. (A) GBS burden (CFU/ml) as determined using perianal swabs collected on days of life 11 and 18 from 3 representative litters (20 pups delivered, 10 survived for swabbing) born to GBS-colonized dams (dotted line is the limit of detection). (B) Kaplan-Meier survival curve of 6 representative litters (n= 42) born to GBS-colonized dams, with the dotted line demarcating LO mortality (after 7 days). (C) Colonic section from a 10-day-old healthy-appearing GBS-colonized.