TITLE:
A Novel LNP-Based Chlamydia Subunit Vaccine Formulation That Induces Th1 Responses without Upregulating IL-17 Provides Equivalent Protection in Mice as Formulations That Induced IL-17 and Th1 Cytokines
AUTHORS:
Melissa A. Boddicker, Robin M. Kaufhold, Kara S. Cox, Bob J. Lucas, Jinfu Xie, Deborah D. Nahas, Sinoeun Touch, Amy S. Espeseth, Kalpit A. Vora, Julie M. Skinner
KEYWORDS:
LNP, Chlamydia, IL-17, Mouse Model, Th1 Cytokines
JOURNAL NAME:
World Journal of Vaccines,
Vol.10 No.4,
November
17,
2020
ABSTRACT: We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from C. muridarum elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to C. muridarum nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P C. muridarum EBs (P C. muridarum EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-γ/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with Chlamydia antigens also showed protection from C. muridarum challenge, by reduction in bacterial shedding for all groups (P