Intradermal Immunization with Wall Teichoic Acid (WTA) Elicits and Augments an Anti-WTA IgG Response that Protects Mice from Methicillin-Resistant Staphylococcus aureus Infection Independent of Mannose-Binding Lectin Status

Abstract

The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

“…In accordance with the observation, immunization with a BSA-conjugated LTA fragment, containing a conserved minimal structure in majority of Gram-positive bacteria, was able to induce opsonic killing of E. faecium E1162 and S. aureus MW2 [81]. Besides, immunization of WTA also elicited an anti-WTA immune response, illustrated by complement-dependent opsonophagocytosis [82,83].…”

Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women

“…A delayed response with an increase of MBL when other components of the innate immune system already are set into action may impose additional, non-beneficial inflammatory responses. Partly supporting this notion are data indicating beneficial effects of low MBL levels in different settings [ 18 – 21 , 23 , 48 – 50 ]. Thus, MBL may have different effects in different situations and in different phases of acute illness.…”

Glycosylation of Staphylococcus aureus cell wall teichoic acid is influenced by environmental conditions

“…S . aureus WTAs have been considered as putative vaccine candidate 4,16 . The pioneer work in that field was conducted by Nabi Biopharmaceuticals with Antigen 336 (Ag336), also named Polysaccharide 336 (PS336).…”