PROTEIN VACCINE AGAINST NEONATAL GROUP B STREPTOCOCCAL INFECTION Immunization experiments in animals and a serological study in humans

Abstract: Infection with group B streptococcus (GBS), an encapsulated bacterium, is an important cause of neonatal morbidity and mortality. Capsular polysaccharides and cell surface proteins of GBS are candidate antigens for development of a human GBS vaccine. Proteins have many advantages as vaccine antigens. The majority of the neonatal infections are caused by strains of capsular serotypes Ia, Ib, II, III, and V. More than 80% of these strains express protein ?, Rib or Rib-like protein. The possible role of the cell surface proteins ? and Rib for a protein-based GBS vaccine was explored in three experimental studies on mice and one observational study of neonates and their mothers. Mice immunized s.c. with a highly purified preparation of Rib mixed with Freund’s adjuvant, were protected against lethal i.p. challenge with each of four GBS strains expressing Rib and partially against a strain expressing ?. Immunization with ? protected against infection with each of two strains expressing ?, but not against a strain expressing Rib. A bivalent vaccine of Rib and ? with alum, an adjuvant commonly used in human vaccines, conferred protection against lethal i.p. challenge with each of four GBS strains of serotypes Ia, Ib, II, and III. Intranasal immunization of mice with protein Rib conjugated to or mixed with cholera toxin B subunit induced systemic and local genital antibody response. This mucosal immunization protected the mice against a lethal i.p. challenge with a GBS type III strain expressing Rib. Sera were collected from neonates with invasive GBS infection, from their mothers and from non-infected referents. There was an association between low levels of naturally acquired antibodies to ? and Rib and invasive infection with strains expressing Rib in sera collected from neonates, which indicates that antibodies to GBS proteins are involved in the defence against GBS disease. The results from the immunization experiments in mice and the serological study in neonates are encouraging for the development of a human vaccine based on GBS cell surface proteins.