Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine

Abstract

Abstract:We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactideco-glycolide) potentiates T helper 1 (Th1) immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP) of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP), characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm), zeta potential (−14.30 mV), apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1) and interleukin (IL)-12p40 (Th1/Th17) than IL-4 and IL-10 (Th2) cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (Ig)G and IgG2a (Th1) than IgG1 (Th2) rMOMP-specific antibodies. Notably, sera from PLGA-rMOMPimmunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C. trachomatis vaccine. The capacity of PLGA-rMOMP to trigger primarily Th1 immune responses in mice promotes it as a highly desirable candidate nanovaccine against C. trachomatis.

Poly(lactic acid)–poly(ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

“…Recombinant MOMP-278 (M278) was cloned as previously reported 15 and encapsulated in PLA-PEG nanoparticles using a modified water/oil/water double emulsion evaporation technique 16,17 and then lyophilized in the presence of 5% trehalose (as a stabilizer) to obtain encapsulated-M278 (PLA-PEG-M278). Phosphate buffered saline (PBS) was similarly encapsulated in PLA-PEG to serve as a negative control (PLA-PEG-PBS).…”

“…UV-Vis was employed to ascertain M278 encapsulation within PLA-PEG as recently described 17,18 . Nanoparticles and bare M278 were each diluted in deionized water and their absorbance and spectral wavelengths were assessed using the DU 800UV/Vis spectrophotometer (Beckman Coulter, Fullerton, CA).…”

“…The encapsulation efficiency (EE) was extrapolated from measurements of the total M278 encapsulated within PLA-PEG as described previously 16,17 and calculated as: EE=A-B/A × 100 %, where A is the total M278 amount, B is the free M278 amount. These measurements were performed three times.…”

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…Chitosan is a chitin-derived polysaccharide and has several properties that make it a useful vaccine delivery system, including its mucoadhesiveness and enhanced penetration capacity across mucosal barriers (188). Two recent studies using recombinant MOMP encapsulated in PLGA demonstrated enhanced induction of Th1 cytokines and cellular and antibody immune responses (189,190). Cambridge et al demonstrated that MOMP was expressed in the tissues and organs of mice that were intramuscularly injected with chitosan nanoparticles containing recombinant MOMP DNA (191).…”

Nanomedicine in the management of microbial infection – Overview and perspectives

“…Synthetic polymers alone do not usually possess an immunostimulatory effect, but can enhance immunization via facilitating the delivery of antigens and/or adjuvants [47]. For example, PLGA nanoparticles incorporating a recombinant major outer membrane protein of Chlamydia trachomatis ( C. trachomatis ) induced elevated numbers of CD4+ and CD8+ T cell subsets and a 64-fold higher Th1 than Th2 antibody titer [170]. Toxoid vaccines, which are based on inactivated bacterial toxins, have been widely used to promote antitoxin immunity for the prophylaxis and treatment of microbial infections.…”