AUTHOR=Verma Richa , Sahu Rajnish , Dixit Saurabh , Duncan Skyla A. , Giambartolomei Guillermo H. , Singh Shree R. , Dennis Vida A. 

TITLE=The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02369

DOI=10.3389/fimmu.2018.02369

ISSN=1664-3224

ABSTRACT=<p>Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of <italic>Chlamydia</italic>)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate <italic>Chlamydia</italic>-specific CD4<sup>+</sup> T-cell immune effector responses. In the present study, we employed the <italic>Chlamydia muridarum</italic> mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced <italic>Chlamydia</italic>-specific adaptive immune responses predominated by IFN-γ along with CD4<sup>+</sup> T-cells proliferation and their differentiation to CD4<sup>+</sup> memory (CD44<sup>high</sup> CD62L<sup>high</sup>) and effector (CD44<sup>high</sup> CD62L<sup>low</sup>) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 &gt; IgG2b &gt; IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of <italic>C. muridarum</italic> in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4<sup>+</sup> T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge.</p>