title: Immunoadjuvant Properties of the Rho Activating Factor CNF1 in Prophylactic and Curative Vaccination against Leishmania infantum.
abstract: There is a need to develop new effective immunoadjuvants for prophylactic or therapeutic vaccines against intracellular pathogens. The activation of Rho GTPases by bacterial cytotoxic necrotizing factor 1 (CNF1) elicits humoral protective responses against protein antigens. Here, we set out to investigate whether CNF1 activity initiates humoral immunity against co-administered parasite antigens and anti-microbial immune signaling. We report that co-administration of wild-type (WT) CNF1 with Leishmania (L.) promastigote antigens at the nasal mucosa triggered prophylactic and curative vaccine responses against this parasite. Vaccination of the mucosa with promastigote lysate antigens combined with WT CNF1 conferred protection against high inoculum L. infantum infection, which reached 82% in the spleen. Immune parameter analysis by antigen recall indicated robust T-helper (Th)1 polarization of immune memory cells, with high IL-2 and IFN-γ production combined with decreased IL-4 production. Additionally, we explored the curative effect of WT CNF1 on previously infected animals. We observed that PL combined with WT CNF1, but not the inactive C866S mutant CNF1 (mCNF1), induced a 58% decrease in the parasite burden in the spleen.
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.|Centre Hospitalier Universitaire de Nice, Laboratoire de Parasitologie-Mycologie, Nice, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Michel
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ferrua
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Munro
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.affiliation: CEA, iBiTecS, SIMOPRO, Paris Saclay University, LabEx LERMIT, Gif sur Yvette, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Mathal
authors.affiliation: CEA, iBiTecS, SIMOPRO, Paris Saclay University, LabEx LERMIT, Gif sur Yvette, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gillet
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.|Centre Hospitalier Universitaire de Nice, Laboratoire de Parasitologie-Mycologie, Nice, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marty
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team "Microbial toxins in host pathogen interactions", Equipe labellisée ligue contre le cancer, Nice, France.|Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000953:Antigens, Protozoan; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D007376:Interleukin-2; C060296:cytotoxic necrotizing factor type 1; D015847:Interleukin-4