Activation of antigen presenting cells and induction of mucosal antibodies by Chlamydia trachomatis outer membrane peptide encapsulated within PLA-PEG nanoparticles

摘要

In pursuit of a vaccine against Chlamydia trachomatis, the most reported bacterial sexually transmitted infection, we recently reported that encapsulation of M278, a peptide derived from the major outer membrane protein of C. trachomatis, within poly (lactic acid)-b-Poly (ethylene glycol) (PLA-PEG) nanoparticles triggered enhanced systemic adaptive immune responses in mice. Here in this study attempts were undertaken to begin to understand the mecahsnim(s) of PLA-PEG capacity to facilitate uptake of antigens by antigen presenting cells (APCs); the ability of encapsulated-M278 to trigger cytokine production by APCs and mucosal antibody immune responses in imminized mice. Our results revealed that in vitro exposure of mouse J774 macrophages and human THP-1 monocytes to varying concentrations of encapsulated-M278 induced marked production of the IL-6 and IL-12 Th1 cytokines, suggesting the ability of encapsulated-M278 to directly interact with and activate APCs. FITC-labelled PLA-PEG nanoparticles were localized in the cytoplasm of macrophages, confirming their phagocytic internalization. BALB/c mice immunized subcutaneously with encapsulated-M278 produced higher IgG and IgG2b M278-specific mucosal antibodies as compared to bare M278 immunized mice, suggesting that PLA-PEG potentiated the capacity of M278 to induce mucosal antibody responses in mice. Collectively, encapsulated-M278 trigerred and potentiated innate and mucosal adaptive immune responses in mice. Studies are ongoing to determine the mechanisms involved in uptake of PLA-PEG by APCs and for enhancement of adaptive immune responses in mice. Key words: Chlamydia;; bacteria;; Major outer membrane protein;; poly (lactic acid)-b-Poly (ethylene glycol);; antibody;; cytokines.