title: A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance.
abstract: BACKGROUND
  A vaccine for Chlamydia trachomatis is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against C. trachomatis that would induce cross-serovar T-cell responses as (i) CD4(+) T cells have been shown in animal models and human studies to be important in chlamydial protection and (ii) antibody responses may be restrictive and serovar specific.
  
  
  METHODS
  A consensus antigen based on over 1,500 major outer membrane protein (MOMP) sequences provided high epitope coverage against the most prevalent C. trachomatis strains in silico. Having designed the T-cell immunogen, we assessed it for immunogenicity in prime-boost regimens. This consensus MOMP transgene was delivered using plasmid DNA, Human Adenovirus 5 (HuAd5) or modified vaccinia Ankara (MVA) vectors with or without MF59(®) adjuvanted recombinant MOMP protein.
  
  
  RESULTS
  Different regimens induced distinct immune profiles. The DNA-HuAd5-MVA-Protein vaccine regimen induced a cellular response with a Th1-biased serum antibody response, alongside high serum and vaginal MOMP-specific antibodies. This regimen significantly enhanced clearance against intravaginal C. trachomatis serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4(+) T-cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection.
  
  
  CONCLUSIONS
  A C. trachomatis vaccine needs to induce a robust cellular response with broad cross-serovar coverage and a heterologous prime-boost regimen may be an approach to achieve this.
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Badamchi-Zadeh
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.affiliation: Los Alamos National Laboratory, Theoretical Division , Los Alamos, NM , USA.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Barinaga
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Walters
authors.affiliation: Department of Infectious Diseases, National Institute of Health , Lisbon , Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nunes
authors.affiliation: Department of Infectious Diseases, National Institute of Health , Lisbon , Portugal.
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Gomes
authors.affiliation: Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institute , Copenhagen , Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Follmann
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Tregoning
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College London , London , UK.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
keywords: Chlamydia trachomatis; DNA vaccines; MVA-vector vaccines; adenovirus-vector vaccines; consensus; mosaic; prime-boost regimens