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Synthesis and preclinical evaluation of glycoconjugate vaccines against group B Streptococcus types VI and VIII
L C Paoletti1, J Pinel, K D Johnson
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. lpaoletti@channing.harvard.edu
Insights
New conjugate vaccines targeting Group B Streptococcus (GBS) types VI and VIII show promise for preventing infant GBS disease. These vaccines effectively induced protective antibodies in animal models, suggesting potential for maternal immunization.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Group B Streptococcus (GBS) types VI and VIII are common in pregnant women in Japan.
- Neonatal GBS disease is a significant concern, and maternal vaccination is a proposed preventive strategy.
- Antibodies against GBS capsular polysaccharide (CPS) are known to be protective.
Purpose of the Study:
- To develop and evaluate conjugate vaccines for GBS types VI and VIII.
- To assess the immunogenicity and protective efficacy of these novel conjugate vaccines.
Main Methods:
- Purified GBS type VI and VIII CPS were coupled to tetanus toxoid to create conjugate vaccines.
- Immunogenicity was assessed by measuring type-specific antibody titers in rabbits.
- Opsonophagocytic activity of elicited antibodies was evaluated in vitro.
- Protective efficacy was determined in a mouse model challenged with GBS.
Main Results:
- The conjugate vaccines induced high-titered, type-specific antibodies in rabbits.
- These antibodies demonstrated opsonically active properties in vitro.
- Vaccinated mice and their offspring showed significant protection against lethal GBS challenge.
Conclusions:
- GBS types VI and VIII conjugate vaccines are immunogenic and protective in preclinical models.
- These vaccines may serve as key components of a multivalent GBS vaccine for regions with prevalent serotypes VI and VIII.
Abstract:
Group B Streptococcus (GBS) types VI and VIII are prevalent among serotypes isolated from pregnant women in Japan. Maternal vaccination with a safe and effective GBS vaccine has been proposed as a rational approach to prevent neonatal GBS disease. Because antibody specific for the capsular polysaccharide (CPS) antigens of GBS is protective, vaccines were developed with purified type VI and VIII CPS coupled to tetanus toxoid. In rabbits the newly synthesized conjugate vaccines elicited high-titered, type-specific antibody that was opsonically active in vitro. Moreover, litters born to mice actively vaccinated with the conjugate vaccines, in contrast to uncoupled CPS or saline, were protected against an ordinarily lethal challenge of GBS of homologous serotype. GBS types VI and VIII conjugate vaccines of the design presented may be important components of a multivalent GBS vaccine for use in regions where these serotypes predominate.