Mucosal Immunization with a Staphylococcus aureus IsdA-Cholera Toxin A₂/B Chimera Induces Antigen-Specific Th2-Type Responses in Mice

Transmission Dynamics of Methicillin-Resistant Staphylococcus aureus in Pigs

“…Recently, Arlian and Tinker (2011) developed a vaccine that combines a S. aureus antigen and an adjuvant, respectively IsdA (which is important in S. aureus colonization) and cholera toxin (CT) A2/B (a potent immunostimulatory molecule that binds to and targets effector cells to the mucosal site). Intranasal administration of this IsdA-CTA2/B chimera in mice induced systemic IgG, mucosal IgA, and cell-mediated response.…”

PilVax, a novel Lactococcus lactis‐based mucosal vaccine platform, stimulates systemic and mucosal immune responses to Staphylococcus aureus

“…17,21 Many of the cell wall-anchored proteins are critical for mucosal colonization: removal of the gene encoding for S. aureus Clumping Factor A led to an impaired ability to colonize the gastrointestinal tract of mice 22 ; comparable studies with ClfB resulted in rapid elimination of bacteria from the nares of human patients compared with the parental strain, 23 with a similar outcome in a mouse model of nasal infection. 24,25 The potential of several cell wallanchored proteins or immunogenic epitopes thereof including ClfA, 26 ClfB, 24 iron-regulated surface protein A, 27,28 IsdB 29 and fibronectin-binding protein (FnBP) 30,31 for mucosal vaccination has been demonstrated in rodent challenge models. Several leading S. aureus vaccine candidates currently in clinical trials comprise multiple components, covering several different aspects of S. aureus virulence, including cell wall-anchored proteins (reviewed in Pozzi et al 32 and Missiakas and Schneewind 33 ).…”

“…A current limitation of the PilVax platform is that only short linear epitopes containing <50 amino acids have been successfully introduced without disrupting pilus polymerization and formation on the surface of L. lactis. Therefore FnBP was chosen as a suitable target because it contains several wellcharacterized conserved linear B-cell epitopes reported to stimulate antibodies that inhibit binding of S. aureus to fibronectin, including an FnBPA/B epitope (FnBP-10) 34 and two peptide sequences that target FnBPA [D1 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) and D3 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) ]. 35 This study aimed to determine whether selected linear B-cell epitopes from S. aureus FnBPA could be successfully engineered into an L. lactis PilVax strain and used as a mucosal vaccine to stimulate production of a robust local antibody response in the nasal and intestinal mucosa.…”

“…This strategy elicited systemic and mucosal antibody responses to a model antigen after intranasal immunization, but has not been tested for its capacity to stimulate protective mucosal immunity. A well-characterized linear B-cell epitope, D3 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) , from the fibronectin-binding protein A of Staphylococcus aureus was successfully introduced into PilVax and delivered intranasally to mice. Specific antipeptide immunoglobulin (Ig) G and IgA antibodies were detected in the serum and respiratory mucosa of vaccinated mice.…”

Viruses and bacteria in Th2‐biased allergic airway disease

“…Even though IL-6Ra high effector memory CD8 + T cells are involved in virus-induced Th2 response, they also trigger IL-5 and IL-13 expressions in response to the bacterial superantigens SEB and TSST-1 (47). In mouse, an adhesion molecule of S. aureus 'iron-regulated surface determinant A' mediated IL-4 secretion from splenocytes (57). In summary, the effect of bacteria on Th2 response especially in upper airways implicates the important role of bacteria in allergic airway diseases.…”