A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant.

Janina Jiang,Kathleen Kelly,Lin-Xi Li,Guangchao Liu,Leonard Rome,Stephen Mcsorley,Valerie Kickhoefer

doi:10.3390/vaccines5010003

Janina Jiang, Kathleen Kelly + Show 5 more

Open Access

https://doi.org/10.3390/vaccines5010003

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Abstract

Chlamydia trachomatis genital 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 a C. muridarum challenge. 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 a Chlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.

Highlights

Chlamydia trachomatis infection is the major cause of bacterial sexually transmitted infections (STIs) with major adverse effects on female reproductive tract health and function
To evaluate the level of protection conferred by polymorphic membrane protein G-1 (PmpG)-vault immunization, mice were immunized by the intranasal route with PmpG-vaults three times at 2 week intervals
In order to determine if delivery of vault-vaccines through the nasal mucosa induce systemic cytokines; IFN-γ, TNF-α, and IL-17 which may only marginally aid in protection from bacterial load as well as tissue specific cellulartract immunity, we examined the cellular immune responses in the in the Genital tracts (GTs)

Summary

Introduction

Chlamydia trachomatis infection is the major cause of bacterial sexually transmitted infections (STIs) with major adverse effects on female reproductive tract health and function. The magnitude of reproductive dysfunction and infertility associated with sexually transmitted C. trachomatis infection is a significant health burden with over 1.5 million infections annually in the United States, a vaccine has not yet been developed [1,2]. Previous research has shown that major histocompatibility complex (MHC) class-II restricted interferon gamma (IFN-γ) producing cluster of differentiation 4 (CD4+ ) T cells are required for protective immunity [5,6,7]. Using mass spectrometry to screen chlamydial peptides eluted from MHC-II peptides, PmpG (polymorphic membrane protein G-1) was identified as conferring strong immunogenicity upon immunization [8]

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