DNA plasmid vaccine carrying Chlamydia trachomatis (Ct) major outer membrane and human papillomavirus 16L2 proteins for anti-Ct infection

Abstract

Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual infection all over the world, yielding tremendous reproductive problems (e.g. infertility and ectopic pregnancy) in the women. This work described the design of a plasmid vaccine that protect mice from Ct infection, and reduce productive tract damage by generating effective antibody and cytotoxic T cell immunity. The vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA plasmid (i.e. pcDNA3.1/MOMP/HPV16L). In transfection, the vaccine expressed the chimeric genes (i.e. MOMP and HPV16L2), as demonstrated via western blot, RT-PCR and fluorescence imaging. In vitro, the vaccine transfected COS-7 cells and expressed the proteins corresponding to the genes carried in the vaccine. Through intramuscular immunization in BALB/c mice, the vaccine induced higher levels of anti-Ct IgG titer, anti-HPV16L2 IgG titer in serum and IgA titer in local mucosal secretions, compared to plasmid vaccines that carry only Ct MOMP multi-epitope or HPV16L2 chimeric component only. In mice intravaginally challenged with Ct, the vaccines pcDNA3.1/MOMP/HPV16L2 generated a higher level of genital protection compared to other vaccine formulations. Additionally, histochemical staining indicated that pcDNA3.1/MOMP/HPV16L2 eliminated mouse genital tract tissue pathologies induced by Ct infection. This work demonstrated that pcDNA/MOMP/HPV16L2 vaccine can protect against Ct infection by regulating antibody production, cytotoxic T cell killing functions and reducing pathological damage in mice genital tract. This work can potentially offer us a new vaccine platform against Ct infection.

Advances in Chlamydia trachomatis Vaccination: Unveiling the Potential of Major Outer Membrane Protein Derivative Constructs

“…Nucleic acid vaccine platforms bypass the need to synthesize proteins in vitro and prompt Th1-skewed responses, which makes them interesting in this MOMP-based C. trachomatis vaccine context [ 1 ]. Some DNA plasmid platforms have been investigated for MOMP-derivative constructs [ 34 , 52 , 59 , 60 , 61 ]. The use of mRNA for C. trachomatis vaccination has not yet been extensively researched [ 1 ].…”

“…VLPs lack genetic material but self-assemble into particles due to their structural proteins. Examples include surface antigens of the Hepatitis B virus [ 52 , 72 , 73 ], the coat protein of the MS2 bacteriophage [ 58 ], and HPV major capsid protein L1 [ 59 , 60 ] or L2 [ 61 ]. These HPV VLPs that deliver a MOMP multi-epitope could potentially protect humans against both C. trachomatis and HPV infections, which is particularly interesting given the correlation between C. trachomatis and HPV infections [ 61 ].…”

“…None None [34,73,84,86,88] Hydrogel suspension [34,36,89,93] Oil-in-water emulsion [80,90,91] Toxin [92] Fusion protein Oil-in-water emulsion [42,78,79,90,91] Vector None [34] Fusion protein + Vector None [27,75,81] Oil-in-water emulsion [83] Nanoparticles None [85,87] On surface nanoparticles [23,24,27,28,[34][35][36][38][39][40]82,88,94,95] Fusion protein + Nanoparticles None [58,72,73] DNA vaccine Plasmid None [34,60,61] Plasmid + Fusion protein + Nanoparticles None [52,[59][60]…”

“…One strain [27,28,36,[38][39][40]42,52,[58][59][60][61]72,73,75,79,81,[85][86][87]89,91,93,94,109] Multiple strains [23,80,82,84,88,90,92,95] Rabbit [78,83] NHP [34,80] Minipig [24,35] C. muridarum and C. trachomatis share considerable homology for MOMP. The conserved neutralizing LNPTIAG epitope that is the subject of many vaccine trials, however, is lacking in MOMP from C. muridarum [23,93].…”