A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections.
Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ- and IL-17A-producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.
['Martin-Cruz|Leticia|L|', 'Sevilla-Ortega|Carmen|C|', 'Benito-Villalvilla|Cristina|C|', 'Diez-Rivero|Carmen M|CM|', 'Sanchez-Ramón|Silvia|S|', 'Subiza|José Luis|JL|', 'Palomares|Oscar|O|']
D000818:Animals D000942:Antigens, Bacterial D000946:Antigens, Fungal D001424:Bacterial Infections D001428:Bacterial Vaccines D015496:CD4-Positive T-Lymphocytes D002181:Candidiasis, Vulvovaginal D002478:Cells, Cultured D018920:Coculture Techniques D016207:Cytokines D003713:Dendritic Cells D005260:Female D005657:Fungal Vaccines D006801:Humans D008213:Lymphocyte Activation D008807:Mice, Inbred BALB C D010641:Phenotype D014552:Urinary Tract Infections D014611:Vaccination D017778:Vaccines, Combined
candida albicans V132 recurrent urinary tract infections (RUTIs) recurrent vulvovaginal candidiasis (RVVCs) dendritic cells trained immunity-based vaccines (TIbVs) polybacterial preparation MV140