title: A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant.
abstract: Chlamydia trachomatisgenital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following aC. muridarumchallenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with aChlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave. CHS 1P-177, Los Angeles, CA 90095, USA. jjiang@mednet.ucla.edu.
authors.forename: Janina
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave. CHS 1P-177, Los Angeles, CA 90095, USA. guangchaoliu@gmail.com.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. vkick@ucla.edu.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Kickhoefer
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. LRome@mednet.ucla.edu.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Rome
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA. lxli@ucdavis.edu.
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Li
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA. sjmcsorley@ucdavis.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave. CHS 1P-177, Los Angeles, CA 90095, USA. kelly@mednet.ucla.edu.|Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. kelly@mednet.ucla.edu.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kelly
keywords: CD4; Chlamydia; infectious diseases; mucosal immunology; tetramer; vaults