Defense From the Group A Streptococcus by Active and Passive Vaccination With the Streptococcal Hemoprotein Receptor

• Published in: The Journal of infectious diseases 2011-06, Vol.203 (11), p.1595-1601
• Main Authors: Huang, Ya-Shu, Fisher, Morly, Nasrawi, Ziyad, Eichenbaum, Zehava
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Antibodies; Antibodies, Bacterial - immunology; Antibodies, Bacterial - metabolism; Antigens; Antiserum; BACTERIA; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacteriology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Hemeproteins - genetics; Hemeproteins - immunology; Immunization; Immunization, Passive; Infections; Injections, Intraperitoneal; Kaplan-Meier Estimate; Lactococcus lactis; Major and Brief Reports; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Microbiology; Phagocytosis; Rabbits; Receptors; Serum Bactericidal Antibody Assay; Streptococcal Infections - prevention & control; Streptococcal Vaccines - administration & dosage; Streptococcal Vaccines - genetics; Streptococcal Vaccines - immunology; Streptococcus; Streptococcus pyogenes; Streptococcus pyogenes - genetics; Streptococcus pyogenes - immunology; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir149

Background. The worldwide burden of the Group A Streptococcus (GAS) primary infection and sequelae is considerable, although immunization programs with broad coverage of the hyper variable GAS are still missing. We evaluate the streptococcal hemoprotein receptor (Shr), a conserved streptococcal protein, as a vaccine candidate against GAS infection. Methods. Mice were immunized intraperitoneally with purified Shr or intranasally with Shr-expressing Lactococcus lactis. The resulting humoral response in serum and secretions was determined. We evaluated protection from GAS infection in mice after active or passive vaccination with Shr, and Shr antiserum was tested for bactericidal activity. Results. A robust Shr-specific immunoglobulin (Ig) G response was observed in mouse serum after intraperitoneal vaccination with Shr. Intranasal immunization elicited both a strong IgG reaction in the serum and a specific IgA reaction in secretions. Shr immunization in both models allowed enhanced protection from systemic GAS challenge. Rabbit Shr antiserum was opsonizing, and mice that were administrated with Shr antiserum prior to the infection demonstrated a significantly higher survival rate than did mice treated with normal rabbit serum. Conclusions. Shr is a promising vaccine candidate that is capable of eliciting bactericidal antibody response and conferring immunity against systemic GAS infection in both passive and active vaccination models.