title: Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine.
abstract: A vaccine is likely the most effective strategy for controlling human chlamydial infections. Recent studies have shown immunization with Chlamydia muridarum major outer membrane protein (MOMP) can induce significant protection against infection and disease in mice if its native trimeric structure is preserved (nMOMP). The objective of this study was to investigate the immunogenicity and vaccine efficacy of Chlamydia trachomatis nMOMP in a nonhuman primate trachoma model. Cynomolgus monkeys (Macaca fascicularis) were immunized systemically with nMOMP, and monkeys were challenged ocularly. Immunization induced high serum IgG and IgA ELISA Ab titers, with Abs displaying high strain-specific neutralizing activity. The PBMCs of immunized monkeys produced a broadly cross-reactive, Ag-specific IFN-gamma response equivalent to that induced by experimental infection. Immunized monkeys exhibited a significant decrease in infectious burden during the early peak shedding periods (days 3-14). However, at later time points, they exhibited no difference from control animals in either burden or duration of infection. Immunization had no effect on the progression of ocular disease. These results show that systemically administered nMOMP is highly immunogenic in nonhuman primates and elicits partially protective immunity against ocular chlamydial challenge. This is the first time a subunit vaccine has shown a significant reduction in ocular shedding in nonhuman primates. A partially protective vaccine, particularly one that reduces infectious burden after primary infection of children, could interrupt the natural trachoma reinfection cycle. This would have a beneficial effect on the transmission between children and sensitized adults which drives blinding inflammatory disease.
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kari
authors.forename: William M
authors.initials: WM
authors.lastname: Whitmire
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Crane
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reveneau
authors.forename: John H
authors.initials: JH
authors.lastname: Carlson
authors.forename: Morgan M
authors.initials: MM
authors.lastname: Goheen
authors.forename: Ellena M
authors.initials: EM
authors.lastname: Peterson
authors.forename: Sukumar
authors.initials: S
authors.lastname: Pal
authors.forename: Luis M
authors.initials: LM
authors.lastname: de la Maza
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008252:Macaca fascicularis / Q000276:immunology*; D008297:Male; D011489:Protein Denaturation; D017186:Titrimetry
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines