Work performed: Prior to project start, SSI performed a phase 1 clinical trial, testing the safety and immunogenicity of a recombinant C. trachomatis vaccine antigen, CTH522. CTH522 covers the highly immunogenic Major Outer Membrane Protein (MOMP) variable (VD4) regions of the four most common C. trachomatis sero-variants and elicits excellent humoral responses. With the aim to broaden CTH522-triggered immunity and so target both extra- and intracellular bacteria, we exploited a number of safe virus-(UNIBAS, UDUS), bacterium- (AB, UNISI) and plasmid-based (UU) vaccine vectors, capable of inducing both potent humoral and cell-mediated immune responses. CTH522 was cloned into these vectors, vaccines were verified for integrity and antigen expression, and subsequently produced at a larger scale to test their immunogenicity. After a comprehensive characterization of immune responses triggered by vaccination with a single or combination of different network-developed vaccines, the protective capacity of four selected vaccine combinations was tested in a preclinical model of C. trachomatis infection at SSI. Two vaccines were shown to provide protection to bacterial challenge, i.e. an E. coli Protein Body vector-based vaccine developed at AB and an LCMV vector-based vaccine developed at UNIBAS, based on vaccine-induced humoral and cellular immunity, respectively. Meanwhile, immunopeptidome analyses performed at UU identified a large number of novel C. trachomatis antigens, in part derived from pathogenesis-associated proteins. A selection of these antigens may be utilized to complement developed vaccines. The analysis of RNAseq data at MBT identified a biomarker for successful vaccination with bacterium-based vaccines. Taken together, the results contribute to a novel generation of C. trachomatis vaccines.
During the five years of the project, all ESR extensively collaborated. Antigen constructs, protocols, peptides, antibodies, a Chlamydia strain, gained knowledge, and newly constructed vectored vaccines were shared between beneficiaries, and ESR visited network partners to test their novel vaccines or to provide help with immunizations in challenge experiments. Moreover, the ESR had the opportunity to attend different courses to enhance both their specific and general knowledge of the vaccine field. They presented their research at a variety of meetings, including VacPath meetings, summer schools, national and international conferences. Based on the generated data, so far 6 manuscripts of single organizations and 5 manuscript joint with network partners have been published in prestigious peer-reviewed journals.
