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Multistage vaccines containing outer membrane, type III secretion system and inclusion membrane proteins protects against a Chlamydia genital tract infection and pathology

Journal article
Authors C. P. O'Meara
C. W. Armitage
D. W. Andrew
A. Kollipara
Nils Y Lycke
A. A. Potter
V. Gerdts
N. Petrovsky
K. W. Beagley
Infection Ldwell Hd
V. P. Immunity
Published in Vaccine
Volume 35
Issue 31
Pages 3883-3888
ISSN 0264-410X
Publication year 2017
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 3883-3888
Language en
Links dx.doi.org/10.1016/j.vaccine.2017.0...
Keywords Chlamydia, Vaccine, ISCOMATRIX, PCEP, CTAl-DD, ADVAX, PLASMODIUM-FALCIPARUM MALARIA, DEVELOPMENTAL CYCLE, TRACHOMATIS, IMMUNITY, IMMUNIZATION, INDUCTION, ADJUVANT, MULTIANTIGEN, EXPRESSION, NYVAC-PF7, Immunology, Medicine, Research & Experimental
Subject categories Immunology

Abstract

Pathogens with a complex lifecycles can effectively evade host immunity in part due to each developmental stage expressing unique sets of antigens. Multisubunit vaccines incorporating signature antigens reflecting distinct developmental stages (multistage vaccines) have proven effective against viral, bacterial and parasitic infection at preventing pathogen evasion of host immunity. Chlamydia trachomatis is characterized by a biphasic extra/intracellular developmental cycle and an acute/persistent (latent) metabolic state; hence a multistage vaccine may prevent immune evasion and enhance clearance. Here we tested the efficacy of a multistage vaccine containing outer membrane (MOMP and PmpG), type three secretion system (T3SS) (CdsF and TC0873) and inclusion membrane proteins (IncA and TC0500) in mice against an intravaginal challenge with Chlamydia muridarum. Comparison of single (eg. MOMP) and double antigen vaccines (eg. MOMP and PmpG), largely targeting the extracellular stage, elicited significant yet comparable protection against vaginal shedding when compared to unimmunized control mice. Utilization of different adjuvants (ISCOMATRIX - IMX, PCEP/polyl:C/IDR1002 - VIDO, CTA1-DD and ADVAX) and numerous immunization routes (subcutaneous - SQ and intranasal - IN) further enhanced protection against infection. However, a multistage vaccine elicited significantly greater protection against vaginal shedding and upper genital tract pathology than vaccines targeting only extra- or intracellular stages. This indicates that protection elicited by a vaccine targeting extracellular chlamydial antigens could be improved by including chlamydial antigen expressed during intracellular phase. (C) 2017 Elsevier Ltd. All rights reserved.

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