Brief communication Vaccines are one of the most significant interventions of medicine, and showed important progress from empirical formulations to rational designs, along the time. Nevertheless, adjuvant development did not experience similar progress [1]. Oligonucleotides containing non-methylated CpG sequences (CpG-ODN) are immunostimulant molecules that are added in vaccine formulations as adjuvants, mostly as phosphorothioate modified ODN (PS-CpG-ODN). These types of bonds give resistance to nucleases leading to a longer in vivo persistence than natural phosphodiester ODN (PO-CpG-ODN). However, the cost of production of PS-CpG-ODN is higher than PO-CpG-ODN, and it has been reported that the long-term use of modified ODN may be associated with adverse side effects in mice, and primates [2]. Those are important factors to consider when developing vaccine systems. Nevertheless, PO-CpG-ODN can be used as adjuvant if complexed with an adequate vehicle, as liposomes [3,4]. Gemini compounds are amphipathic molecules formed by a hydrophobic moiety containing two hydrocarbon chains of variable length, and two hydrophilic portions that can be peptides, among other low molecular weight groups [5]. We developed a series of monomeric lipopeptides that function as DNA and protein carriers, called [AGn-Cm]2, where AGn is the peptidic polar head group and Cm is the non-polar region, attached to the peptide N-terminus [5]. A cysteine in the peptide can form a disulphide bridge with another monomer and generates the gemini lipopeptide by dimerization at physiological pH. Based on their ability to form complexes with negatively charged DNA, some of them are transfection reagents with high efficiency [5,6]. However, the use of these molecules in adjuvant formulations has not been described. In this study, we developed formulations based on cationic gemini lipopeptides and
The control of the worldwide spread of sexually transmitted Chlamydia trachomatis (Ct) infection urgently demands the development of a preventive vaccine. In this work, we designed a vaccine based on a fragment of polymorphic protein D (FPmpD) that proved to be immunogenic enough to generate a robust systemic and mucosal IgG humoral immune response in two strains of mice. We used a heterologous prime-boost strategy, including simultaneous systemic and mucosal administration routes. The high titers of anti-PmpD antibodies elicited by this immunization scheme did not affect murine fertility. We tested the vaccine in a mouse model of Ct intravaginal infection. Anti-PmpD antibodies displayed potent neutralizing activity in vitro and protective effects in uterine tissues in vivo. Notably, the humoral immune response of PmpD-vaccinated mice was faster and stronger than the primary immune response of non-vaccinated mice when exposed to Ct. FPmpD-based vaccine effectively reduced Ct shedding into cervicovaginal fluids, bacterial burden at the genitourinary tract, and overall infectivity. Hence, the FPmpD-based vaccine might constitute an efficient tool to protect against Ct intravaginal infection and decrease the infection spreading.
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