Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity
“…Human SIgA were shown to bind to the DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) and be internalized suggesting that binding to this receptor is a mechanism used by SIgA to prime adaptive immune responses in mucosal tissues (89). This concept was further confirmed by murine studies, which showed that when used as vaccine antigen delivery system, SIgA interacts specifically with M cells present in the GALT or NALT and delivers antigen to mucosal DC for optimal induction of antigen-specific mucosal and systemic immunity (90, 91). …”
Section: Vaccine Adjuvants and Delivery Systems For Induction Of Mmentioning
Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and the enzymes of host or microbial origin. Production of SIgA is finely regulated and distinct T-independent and T-dependent mechanisms orchestrate immunoglobulin heavy chain α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for IgA responses. The efficacy of such vaccines relies on the identification/engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.
“…Human SIgA were shown to bind to the DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) and be internalized suggesting that binding to this receptor is a mechanism used by SIgA to prime adaptive immune responses in mucosal tissues (89). This concept was further confirmed by murine studies, which showed that when used as vaccine antigen delivery system, SIgA interacts specifically with M cells present in the GALT or NALT and delivers antigen to mucosal DC for optimal induction of antigen-specific mucosal and systemic immunity (90, 91). …”
Section: Vaccine Adjuvants and Delivery Systems For Induction Of Mmentioning
Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and the enzymes of host or microbial origin. Production of SIgA is finely regulated and distinct T-independent and T-dependent mechanisms orchestrate immunoglobulin heavy chain α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for IgA responses. The efficacy of such vaccines relies on the identification/engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.
“…In order to provide an optimal defense against luminal noxa luminal IgA are continuously sampled at the epithelium and transported to the basolateral side, where it is inspected by immune cells whether it is loaded with antigen or not. If this is the case, an immune response is mounted or boosted (191). Although this type of transcytotic event has been attributed primarily to M cells, the set-up of the ragweed-study rather precludes that route in this specific case in as much as a human IgA1 against Amb a I was used and this type of IgA does not bind to murine M cells (172).…”
Section: Siga In Chronic Inflammation Of the Lungmentioning
“…Serum CXCL13 levels were determined in 10-fold diluted samples using a DuoSet ELISA Mouse CXCL13 Kit (R&D Systems). ELISPOT assays were performed with mouse splenocytes as described previously (16).…”
Section: In Vivo Immunogenicity Of Vaccine Formulationsmentioning
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8 T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced T1/T2 profile in mice. Collectively, these data reveal the potential utility of chimeric adjuvants with synergistic activities mediated via TLRs.
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