AUTHOR=Badamchi-Zadeh Alexander , McKay Paul F. , Korber Bette T. , Barinaga Guillermo , Walters Adam A. , Nunes Alexandra , Gomes João Paulo , Follmann Frank , Tregoning John S. , Shattock Robin J. 

TITLE=A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance

JOURNAL=Frontiers in Immunology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00162

DOI=10.3389/fimmu.2016.00162

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>A vaccine for <italic>Chlamydia trachomatis</italic> is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against <italic>C. trachomatis</italic> that would induce cross-serovar T-cell responses as (i) CD4<sup>+</sup> 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.</p></sec><sec id="ST2"><title>Methods</title><p>A consensus antigen based on over 1,500 major outer membrane protein (MOMP) sequences provided high epitope coverage against the most prevalent <italic>C. trachomatis</italic> strains <italic>in silico</italic>. 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<sup>®</sup> adjuvanted recombinant MOMP protein.</p></sec><sec id="ST3"><title>Results</title><p>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 <italic>C. trachomatis</italic> serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4<sup>+</sup> T-cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection.</p></sec><sec id="ST4"><title>Conclusion</title><p>A <italic>C. trachomatis</italic> 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.</p></sec>