Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus

Abstract

Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus is a promising strategy for the prevention of perinatal infections caused by group B streptococci. To explore the feasibility of this strategy, we vaccinated 40 pregnant women at a mean gestation of 31 weeks with a single 50-microgram dose of the Type III capsular polysaccharide of group B streptococcus. The only adverse effect detected was a mild local reaction in nine women (22 percent). Of the 35 women with low or unprotective antibody levels before immunization (less than 2 micrograms per milliliter), 20 (57 percent) responded to the vaccine. The geometric mean antibody level rose from 1.3 to 7.1 micrograms per milliliter four weeks after vaccination (P less than 0.02), and these levels persisted at delivery and three months post partum. Sixty-two percent of the vaccine-induced immunoglobulin in the mothers was IgG, which readily crosses the placenta. Infant antibody levels in cord serum correlated directly with maternal antibody levels at delivery (r = 0.913, P less than 0.001). Of the 25 infants born to women who responded to the vaccine, 80 percent continued to have protective levels of antibody at one month of age and 64 percent had protective levels at three months. Serum samples from infants with greater than or equal to 2 micrograms of antibody to Type III group B streptococcus per milliliter uniformly promoted efficient opsonization, phagocytosis, and bacterial killing in vitro of Type III strains. This effect could be mediated exclusively by the alternative complement pathway. Although this vaccine with an overall response rate of 63 percent is not optimally immunogenic, we conclude that maternal immunization is feasible and can provide passive immunity against systemic infection with Type III group B streptococcus in the majority of newborns. Larger trials with better vaccines will be required to evaluate the safety and clinical effectiveness of this strategy.

PIP: Of the 11,000 cases of neonatal infection with group B streptococcus that occur each year in the US, 2/3 are caused by Type III strains. Although only 63% of adults produce an immune response to the Type III capsular polysaccharide of group B streptococcus, the high infant morbidity from this strain makes the development even of a less than optimal maternal vaccine worthwhile if the antibodies can cross the placental barrier and confer immunity to the infant. 40 pregnant women, aged 21-39, in the 26th to the 36th week of pregnancy, were immunized subdermally with 50 mc of Type III capsular polysaccharide of group B streptococcus. 63% of the women responded to the vaccine, and 62% of the antibodies produced in response to the vaccine were IgG, which readily crosses the placental barrier. Serum samples from the 25 infants born to the responders contained more than 21.8 mc per milliliter of antibody to Type III group B streptococcus at birth. 64% of these infants' serum still showed protective antibody levels at 3 months of age. These antibody levels were sufficiently high to activate the alternative complement pathway required for the opsonization and phagocytosis of Type III strains. Thus, even though this vaccine is only 63% immunogenic, it can prevent a substantial number of group B streptococcus infections in infants.