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

• Published in: Vaccine 2017-07, Vol.35 (31), p.3883-3888
• Main Authors: O'Meara, Connor P, Armitage, Charles W, Andrew, Dean W, Kollipara, Avinash, Lycke, Nils Y, Potter, Andrew A, Gerdts, Volker, Petrovsky, Nikolai, Beagley, Kenneth W
• Format: Article
• Language: English
• Subjects: ADJUVANT; Adjuvants; Adjuvants, Immunologic - administration & dosage; ADVAX; Allergy and Immunology; Animals; Antigens; Bacteria; Bacterial Proteins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Chlamydia; Chlamydia Infections - prevention & control; Chlamydia muridarum - immunology; CTA1-DD; CTAl-DD; DEVELOPMENTAL CYCLE; Developmental stages; E coli; EXPRESSION; Female; Females; Genital tract; Immune clearance; IMMUNITY; IMMUNIZATION; Immunization Schedule; Immunologi; Immunology; IncA protein; INDUCTION; Infections; Intracellular; ISCOMATRIX; Major outer membrane protein; Medicine; Membrane proteins; Membrane Proteins - immunology; Membranes; Mice; Mice, Inbred BALB C; MULTIANTIGEN; Multistage; NYVAC-PF7; Parasitic diseases; Pathogens; Pathology; PCEP; PLASMODIUM-FALCIPARUM MALARIA; Polyinosinic:polycytidylic acid; Proteins; Reproductive Tract Infections; Research & Experimental; Sexually transmitted diseases; Shedding; Statistical analysis; STD; TRACHOMATIS; Tuberculosis; Type III Secretion Systems - immunology; Vaccine; Vaccines; Vagina
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.05.063

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/polyI: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.