Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge
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 bolst...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.660932/full |
| _version_ | 1818435465982771200 |
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| author | Rajnish Sahu Saurabh Dixit Richa Verma Skyla A. Duncan Lula Smith Guillermo H. Giambartolomei Shree R. Singh Vida A. Dennis |
| author_facet | Rajnish Sahu Saurabh Dixit Richa Verma Skyla A. Duncan Lula Smith Guillermo H. Giambartolomei Shree R. Singh Vida A. Dennis |
| author_sort | Rajnish Sahu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T16:53:19Z |
| format | Article |
| id | doaj.art-78e0de3165c943a5b8f97f0f028f771a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T16:53:19Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-78e0de3165c943a5b8f97f0f028f771a2022-12-21T22:54:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.660932660932Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-ChallengeRajnish Sahu0Saurabh Dixit1Richa Verma2Skyla A. Duncan3Lula Smith4Guillermo H. Giambartolomei5Shree R. Singh6Vida A. Dennis7Center for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesInstituto de Inmunología, Genética y Metabolismo (INIGEM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesCenter for NanoBiotechnology Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, United StatesRecently 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.660932/fullChlamydia muridarummajor outer membrane proteinnanovaccinePLGA nanoparticlesneutralizing antibodies |
| spellingShingle | Rajnish Sahu Saurabh Dixit Richa Verma Skyla A. Duncan Lula Smith Guillermo H. Giambartolomei Shree R. Singh Vida A. Dennis Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge Frontiers in Immunology Chlamydia muridarum major outer membrane protein nanovaccine PLGA nanoparticles neutralizing antibodies |
| title | Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge |
| title_full | Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge |
| title_fullStr | Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge |
| title_full_unstemmed | Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge |
| title_short | Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge |
| title_sort | encapsulation of recombinant momp in extended releasing plga 85 15 nanoparticles confer protective immunity against a chlamydia muridarum genital challenge and re challenge |
| topic | Chlamydia muridarum major outer membrane protein nanovaccine PLGA nanoparticles neutralizing antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.660932/full |
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