title: Induction of protection in mice against a respiratory challenge by a vaccine formulated with the Chlamydia major outer membrane protein adjuvanted with IC31®.
abstract: IC31(®), a novel adjuvant, has been shown to be effective by increasing the levels of IFN-γ in animal models when delivered with several antigens. Here, we tested the ability of IC31(®), to enhance the protective ability of the Chlamydia trachomatis native major outer membrane protein (nMOMP). BALB/c mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with nMOMP+IC31(®). Another group of animals was immunized with nMOMP+Alum and as a negative control mice were immunized with ovalbumin (Ova)+IC31(®). Animals immunized with nMOMP+IC31(®) developed high Chlamydia-specific IgG titers. The serum levels of IgG1 were higher than those of the IgG2a. T cells, from the spleens of mice immunized with IC31(®)-adjuvanted nMOMP demonstrated a strong lymphoproliferative reaction to Chlamydia elementary bodies (EB) compared with the groups immunized with nMOMP+Alum or Ova+IC31(®). A similar comparison between these groups of mice revealed that the levels of IFN-γ in the supernatants from stimulated T-cells were significantly higher in animals immunized with nMOMP+IC31(®). Following an intranasal challenge with C. trachomatis, the mice immunized with IC31(®)-adjuvanted nMOMP showed significant protection. The change in body weight, an indication of the severity of the infection, was significantly less reduced in mice immunized with nMOMP+IC31(®). Furthermore, the weight of the lungs, as well as the pulmonary Chlamydia burden, was significantly lower in the animals immunized with nMOMP+IC31(®) when compared with the groups immunized with nMOMP+Alum or with Ova+IC31(®). In conclusion, these results provide the rationale for further preclinical testing of IC31(®) using other chlamydial antigens, and support the potential evaluation of this adjuvant in human vaccines against Chlamydia.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical Sciences 1, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Cheng
authors.forename: Maria I
authors.initials: MI
authors.lastname: Cruz-Fisher
authors.forename: Delia
authors.initials: D
authors.lastname: Tifrea
authors.forename: Sukumar
authors.initials: S
authors.lastname: Pal
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wizel
authors.forename: Luis M
authors.initials: LM
authors.lastname: de la Maza
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001835:Body Weight; D049109:Cell Proliferation; D002690:Chlamydia Infections / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000472:pathogenicity; D004338:Drug Combinations; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D009842:Oligopeptides / Q000008:administration & dosage*; D018272:Porins / Q000008:administration & dosage / Q000276:immunology*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004338:Drug Combinations; C544002:IC31 adjuvant; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D018272:Porins; C071677:omp1 protein, Chlamydia trachomatis; D007371:Interferon-gamma