Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge
| Autor: | Saurabh Dixit, Guillermo H. Giambartolomei, Skyla A. Duncan, Shree R. Singh, Rajnish Sahu, Vida A. Dennis, Lula Smith, Richa Verma |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
02 engineering and technology Mice CHLAMYDIA MURIDARUM Immunology and Allergy Original Research Infectivity Mice Inbred BALB C Chlamydia biology Vaccination purl.org/becyt/ford/3.1 [https] 021001 nanoscience & nanotechnology Antibodies Bacterial Recombinant Proteins Bacterial Vaccines Cytokines nanovaccine Female purl.org/becyt/ford/3 [https] Antibody 0210 nano-technology Bacterial Outer Membrane Proteins lcsh:Immunologic diseases. Allergy Chlamydia muridarum Immunology MAJOR OUTER MEMBRANE PROTEIN chemical and pharmacologic phenomena NANOVACCINE NEUTRALIZING ANTIBODIES 03 medical and health sciences Immune system Adjuvants Immunologic PLGA NANOPARTICLES medicine Animals Avidity neutralizing antibodies Genitalia business.industry major outer membrane protein Chlamydia Infections medicine.disease biology.organism_classification 030104 developmental biology Immunization Delayed-Action Preparations PLGA nanoparticles biology.protein Nanoparticles Nasal administration business lcsh:RC581-607 Antimicrobial Cationic Peptides |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.660932/full |
| Popis: | 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. Fil: Sahu, Rajnish. University of Alabama at Birmingahm; Estados Unidos Fil: Dixit, Saurabh. University of Alabama at Birmingahm; Estados Unidos Fil: Verma, Richa. University of Alabama at Birmingahm; Estados Unidos Fil: Duncan, Skyla A.. University of Alabama at Birmingahm; Estados Unidos Fil: Smith, Lula. University of Alabama at Birmingahm; Estados Unidos Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Singh, Shree R.. University of Alabama at Birmingahm; Estados Unidos Fil: Dennis, Vida A.. University of Alabama at Birmingahm; Estados Unidos |
| Databáze: | OpenAIRE |
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