Design of a vaccine to immunize neonates against G.. (DEVANI)
Design of a vaccine to immunize neonates against GBS infections through a durable maternal immune response
Start date: Jan 1, 2008,
End date: Jun 30, 2011
"Direct vaccination cannot prevent diseases that affect neonates in the first days of life. Group B Streptococcus (GBS) is the major cause of neonatal septicemia and meningitis affecting up to one in every thousand live births. Over 80% of cases occur in the first 7 days after birth and the remaining 20% of disease occurs between 8-90 days after birth. Studies carried out in the USA indicate that high titres of maternal antibody to GBS capsular polysaccharides (CPS) correlate with reduced risk of disease in neonates suggesting that maternal immunization may be an effective strategy for delivery of a protective immune response to the child in this early period. The overall objective of this proposal is to design immunization strategies capable of inducing strong durable and placentally transferable protective immune responses against GBS in women in order to fill this gap in early infancy when direct immunization is not possible. Starting with the genome sequence of 8 strains of GBS, Novartis scientists have identified three proteins that confer protection against lethal challenge in neonatal mice from immunized females. Combinations of CPS conjugates plus the recombinant proteins conferred protection against 12 of 12 GBS strains representing the major disease causing serotypes. In order to translate this research into a viable vaccine it will be necessary to identify appropriate adjuvant and delivery systems capable of inducing a protective response which will last through pregnancy. In order to select the serotypes of CPS to include in the vaccine, it will be necessary to understand the serotype distribution of GBS disease in Europe. Furthermore, an immune surrogate of protection will be required to replace efficacy trials. This proposal will address these issues by evaluating adjuvant and delivery in mouse models of disease and by analysis of maternal antibody levels and strain characteristics in cases versus controls obtained from several countries in Europe"
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