Immunoadjuvant Properties of the Rho Activating Factor CNF1 in Prophylactic and Curative Vaccination against Leishmania infantum

• Published in: PloS one 2016-06, Vol.11 (6), p.e0156363-e0156363
• Main Authors: Michel, Grégory, Ferrua, Bernard, Munro, Patrick, Boyer, Laurent, Mathal, Nassim, Gillet, Daniel, Marty, Pierre, Lemichez, Emmanuel
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Analysis; Animals; Antigens; Antigens, Protozoan - immunology; Antiinfectives and antibacterials; Bacteria; Bacterial infections; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Bacteriology; Biology and Life Sciences; Cancer; Cell Behavior; Cellular Biology; Cholera; Computer memory; Cytotoxic necrotizing factor 1; Cytotoxicity; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Female; G proteins; Gene expression; Health aspects; Humoral immunity; Immunity; Immunity, Humoral - immunology; Immunity, Humoral - physiology; Immunological memory; Infections; Inoculum; Interferon; Interleukin 2; Interleukin 4; Interleukin-2 - metabolism; Interleukin-4 - metabolism; Laboratory animals; Leishmania; Leishmania infantum; Leishmania infantum - immunology; Leishmania infantum - pathogenicity; Life Sciences; Medicine and Health Sciences; Memory cells; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Microorganisms; Mucosa; Parasites; Parasitic diseases; Prevention; Research and Analysis Methods; Signaling; Spleen; Subcellular Processes; T-Lymphocytes - immunology; Tetanus; Toxins; Tropical diseases; Vaccination; Vaccination - methods; Vaccines; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156363

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.