Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge

Abstract

Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.

Efficacy of Pgp3 vaccination for Chlamydia urogenital tract infection depends on its native conformation

“…Although the role of specific humoral immune responses in controlling chlamydial infection is controversial, the role of Th1 cells and their signature cytokine IFN-γ is well defined ( 27 – 29 ). The Pgp3 monomer and trimer may differ in conformational structure, but the primary amino acid sequence and linear epitopes are identical, and Th1 cell activation relies on antigen-presenting cells (APC) presenting linear epitopes.…”

Peritoneal Administration of a Subunit Vaccine Encapsulated in a Nanodelivery System Not Only Augments Systemic Responses against SARS-CoV-2 but Also Stimulates Responses in the Respiratory Tract

“…For instance, intraperitoneal immunization with poly-(I:C) adjuvanted inactivated SARS-CoV strongly elevated antigen-specific IgA and IgG at multiple sites of the mucosa [47]. More recently, delivery of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) containing the recombinant major outer membrane protein (rMOMP) of C. muridarum to mice via subcutaneous injection efficiently protected mice from genital bacterial challenge by inducing strong IgG but low IgA responses in the mucosal tissues [48]. In line with these reports, we revealed here that the mucosal antibody responses were markedly augmented in the lungs and BALs of mice peritoneally immunized with S-TMC NPs.…”

Immune modulating nanoparticles for the treatment of ocular diseases

“…Rajnish Sahu et al then summarized polymeric NPs used in vaccines in recent years. As mentioned above, PLGA NPs loaded with MOMP enhance adaptive responses with high biocompatibility and bioavailability, including the activation of Th1 cytokines and Th1 and Th2 antibodies [48]. In addition, cSAPs formed by a combination of PLGA, L-histidine and PEG have been shown to increase cell surface adhesion through charge conversion (moderately negative charge at pH 7.4 and converted to cationic charge at pH below 6.5 due to protonation of the PLH imidazole group) and ring-opening reactions that release UV-Ct, thereby promoting IFN-γ production, a robust antibody response, and CD4 + T-cell activation, which demonstrated enhanced mucosal immunity in mice with long-term protective immunity [36].…”

“…Poly lactic acid-co-poly ethylene glycol (PLA-PEG) is the formation of a PEG-surrounding poly lactic acid (PLA) core, which has the advantages of improving hydrophilicity, increasing drug loading capacity, delaying drug release, and delaying biodegradation. By encapsulating the recombinant peptides of MOMP (M278), PLA-PEG has been shown to activate the production of T-cell specific T helper (Th) 1 cytokines (interferon (IFN)-γ, IL-2), serum Th1 (IgG2a) and Th2 (IgG1, IgG2b) antibodies, which indicates an enhanced adaptive immune response [48].…”