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

SAHU, RAJNISH; DIXIT, SAURABH; VERMA, RICHA; DUNCAN, SKYLA A.; SMITH, LULA; GIAMBARTOLOMEI, GUILLERMO H.; SINGH, SHREE R.; DENNIS, VIDA A.

Frontiers in Immunology

Frontiers Media SA

Año: 2021 vol. 12

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 immuneeffectormechanisms to confer protective efficacy in mice against a Chlamydiamuridarum genital challenge and re-challenge. Female BALB/c mice received threeimmunizations, either subcutaneously (SC) or intranasally (IN), before receiving anintravaginal 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 withenhanced protection after a re-challenge, especially in the SC mice. The nanovaccineinduced robust antigen-specific Th1 (IFN-g, 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 andmucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted.Importantly, immunized mice produced highly functional Th1 avidity and serumantibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro thatcorrelated with their respective protection levels. The SC, rather than the IN immunizationroute, triggered higher cellular and humoral immune effectors that improved miceprotection against genital C. muridarum. We report for the first time that the extendedreleasingPLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity inmice against genital Chlamydia and advances the potential towards acquiring a nanobasedChlamydia vaccine.