Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both...

Area of Science:

• Microbiology and Immunology
• Neonatal Infectious Diseases
• Vaccinology and Immunotherapy

Background:

• Group B Streptococcus (GBS) is a significant cause of neonatal infections, persisting despite antibiotic prophylaxis.
• Neonates have underdeveloped immune systems and limited antibody transfer, increasing susceptibility to GBS.
• Immune prophylaxis is a promising strategy to protect vulnerable neonates from GBS infections.

Purpose of the Study:

• To evaluate the protective efficacy of antibodies against GBS cell wall-anchored proteins (FbsA, BibA, PilA, PilB).
• To determine the mechanisms of protection conferred by these antibodies, including opsonophagocytosis and functional blockade.
• To assess the potential of antibody-based immune prophylaxis for preventing GBS infections in neonates.

Main Methods:

• Passive immunization and lethal challenge studies were conducted using rabbit polyclonal and murine monoclonal antibodies.
• Antibody efficacy was tested against multiple GBS strains.
• In vitro opsonophagocytic killing (OPK) assays and in vivo studies with antibody fragments (Fab) were used to elucidate mechanisms.

Main Results:

• Single antibodies provided strain-dependent protection; combinations offered superior, broad-spectrum efficacy against all tested GBS strains.
• Antibodies targeting pilus proteins (PilA, PilB) induced potent OPK activity and required the Fc domain for in vivo protection.
• Antibodies against FbsA and BibA lacked OPK activity but their Fab fragments conferred protection, indicating functional blockade as the mechanism.

Conclusions:

• Antibodies targeting GBS cell wall proteins, particularly pilus proteins, are effective in passive immunization.
• Both Fc-dependent mechanisms (opsonophagocytosis) and Fc-independent mechanisms (functional blockade) contribute to protection.
• These findings support the development of human monoclonal antibody-based prophylaxis for premature neonates at high risk for GBS infection.