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Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein
L C Madoff1, J L Michel, E W Gong
1Channing Laboratory, Brigham & Women's Hospital, Boston, Massachusetts.
Insights
Group B Streptococcus (GBS) causes neonatal sepsis. Immunizing with the GBS beta C protein antigen protected offspring from lethal GBS infection in mice, showing promise for preventing neonatal disease.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis in the US.
- Preventing neonatal GBS disease is a significant public health challenge.
- Immunization of women of childbearing age is a potential strategy for prevention.
Purpose of the Study:
- To evaluate the efficacy of the GBS beta C protein as a vaccine candidate.
- To determine if active immunization with beta C protein protects offspring from GBS infection.
Main Methods:
- Purification of the GBS beta C protein antigen.
- Immunization of rabbits with beta C protein and collection of immune sera.
- Passive transfer of immune sera to pregnant mice and challenge of neonatal pups with GBS.
- Active immunization of adult female mice with beta C protein prior to mating and challenge of their offspring with GBS.
Main Results:
- Immune antiserum from rabbits protected 68% of neonatal mouse pups against GBS challenge.
- Immune serum facilitated opsonophagocytic killing of GBS strains expressing beta C protein.
- Active immunization of dams with beta C protein conferred dose-dependent protection to their offspring, with 96% survival in the high-dose group.
Conclusions:
- The GBS beta C protein is a promising vaccine candidate for preventing neonatal GBS disease.
- Active immunization with the beta C protein confers protective immunity to offspring against lethal GBS infection.
Abstract:
Group B streptococci (GBS) cause the majority of cases of neonatal sepsis and meningitis in the United States. Immunization of women of childbearing age is one strategy under consideration for the prevention of neonatal disease. The beta C protein, a 130-kDa antigen present in many clinical isolates of GBS, was purified from GBS by extraction into sodium dodecyl sulfate (SDS)-containing buffer, preparative SDS-polyacrylamide gel electrophoresis, and electroelution. Purified beta C protein antigen (25 micrograms) with Freund's adjuvant was used to immunize rabbits. Rabbits developed enzyme-linked immunosorbent assay titers of > 1:1.6 x 10(6), and sera from immunized rabbits were administered to pregnant mice. Their neonatal pups were then challenged with a strain of GBS expressing beta C protein; 68% of these pups were protected by immune antiserum, whereas no controls were protected (P < 0.001). The immune serum (diluted 1:100) facilitated opsonophagocytic killing of GBS strains expressing the beta C protein but not those that do not express the antigen (mean log kill +/- standard deviation = 0.71 +/- 0.8 log10 CFU for beta+ strains and 0.09 +/- 0.2 for beta- strains; P = 0.02). In subsequent experiments, adult female mice were actively immunized with two doses of 2, 5, or 10 micrograms of beta C protein 2 months prior to mating. One- to two-day-old offspring of these dams were challenged with GBS and were protected in a dose-dependent manner, with 96% survival in the high-dose (10-micrograms) group and 20% survival in a sham-immunized control group (P < 0.001). Thus, active immunization of mice with the GBS beta C protein confers protection against lethal infection with beta+ GBS to their offspring.