Immunization with a polyprotein vaccine consisting of the T-Cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis.

Abstract:

:Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Coler RN,Skeiky YA,Bernards K,Greeson K,Carter D,Cornellison CD,Modabber F,Campos-Neto A,Reed SG

doi

10.1128/iai.70.8.4215-4225.2002

keywords:

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

4215-25

issue

8

eissn

0019-9567

issn

1098-5522

journal_volume

70

pub_type

杂志文章
  • Characterization of murine monoclonal and murine, rabbit, and human polyclonal antibodies against chlamydial lipopolysaccharide.

    abstract::Murine monoclonal and rabbit, murine, and human polyclonal antibodies against chlamydial lipopolysaccharide (LPS) were characterized by the passive hemolysis and passive hemolysis inhibition assays and by absorption experiments with LPSs of Chlamydia psittaci, Chlamydia trachomatis, and a recombinant strain of Salmone...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.58.1.205-213.1990

    authors: Brade L,Holst O,Kosma P,Zhang YX,Paulsen H,Krausse R,Brade H

    更新日期:1990-01-01 00:00:00

  • Identification and distribution of immunocompetent cells in inflamed gingiva of human chronic periodontitis.

    abstract::Advanced human periodontitis is considered to be a B-cell lesion, but the cellular infiltrate contains several cell types, the distribution of which has not been determined. This experiment was designed to characterize and identify the immunocompetent cells on histological sections and in eluates from diseased human g...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.41.1.365-374.1983

    authors: Okada H,Kida T,Yamagami H

    更新日期:1983-07-01 00:00:00

  • Cellular responses to mycobacterial antigens are present in bronchoalveolar lavage fluid used in the diagnosis of sarcoidosis.

    abstract::Considerable evidence supports the concept that CD4(+) T cells are important in sarcoidosis pathogenesis, but the antigens responsible for the observed Th1 immunophenotype remain elusive. The epidemiologic association with bioaerosols and the presence of granulomatous inflammation support consideration of mycobacteria...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00142-09

    authors: Oswald-Richter KA,Culver DA,Hawkins C,Hajizadeh R,Abraham S,Shepherd BE,Jenkins CA,Judson MA,Drake WP

    更新日期:2009-09-01 00:00:00

  • Immediate cytotoxicity of Chlamydia trachomatis for mouse peritoneal macrophages.

    abstract::The toxicity of Chlamydia trachomatis was studied with mouse peritoneal macrophage culture. Inoculation of 30 inclusion-forming units of trachoma B/TW-5/OT organisms and 250 inclusion-forming units of lymphogranuloma venereum L2/434/Bu organisms per cell caused immediated toxicity, with the killing of 40 to 90% of the...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.20.3.613-618.1978

    authors: Kuo CC

    更新日期:1978-06-01 00:00:00

  • Genetic relationships between clinical isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: characterization of "Atypical" pneumococci and organisms allied to S. mitis harboring S. pneumoniae virulence factor-encoding genes

    abstract::The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distin...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.3.1374-1382.2000

    authors: Whatmore AM,Efstratiou A,Pickerill AP,Broughton K,Woodard G,Sturgeon D,George R,Dowson CG

    更新日期:2000-03-01 00:00:00

  • Cell-mediated immunity to varicella-zoster virus demonstrated by viral inactivation with human leukocytes.

    abstract::Cell-mediated immunity to varicella-zoster (V-Z) virus in persons immune to varicella has been demonstrated, using a tissue culture technique. Cell-mediated immunity was reflected by the ability of peripheral leukocytes (lymphocytes and monocytes) from human donors to inactivate V-Z virus. Leukocytes were stimulated b...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.13.6.1549-1553.1976

    authors: Gershon AA,Steinberg S,Smith M

    更新日期:1976-06-01 00:00:00

  • Purification and characterization of an extracellular secretogenic non-membrane-damaging cytotoxin produced by clinical strains of Vibrio cholerae non-O1.

    abstract::Some clinical strains of Vibrio cholerae non-O1 produce an extracellular factor that evokes a rapid and dramatic cytotoxic response which manifests as cell rounding of Chinese hamster ovary (CHO) and HeLa cells without accompanying membrane damage. This study was performed to establish the identity of the non-membrane...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.64.8.3101-3108.1996

    authors: Saha PK,Koley H,Nair GB

    更新日期:1996-08-01 00:00:00

  • Trehalose 6,6'-dimycolate (Cord factor) enhances neovascularization through vascular endothelial growth factor production by neutrophils and macrophages.

    abstract::Trehalose 6,6'-dimycolate (TDM) plays important roles in the development of granulomatous inflammation during infection with Mycobacterium spp., Rhodococcus spp., etc. To reveal the augmenting effect of TDM on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granuloma...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.4.2043-2052.2000

    authors: Sakaguchi I,Ikeda N,Nakayama M,Kato Y,Yano I,Kaneda K

    更新日期:2000-04-01 00:00:00

  • The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice.

    abstract::The virulence plasmids of Salmonella typhimurium and other invasive Salmonella serovars have long been associated with the ability of these bacteria to cause systemic infection beyond the intestines in orally inoculated animals. Genetic analysis of virulence genes on the high-molecular-weight plasmids has revealed tha...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.61.2.504-511.1993

    authors: Gulig PA,Doyle TJ

    更新日期:1993-02-01 00:00:00

  • Cloning and sequencing of the immunoglobulin A1 protease gene (iga) of Haemophilus influenzae serotype b.

    abstract::Secretion of immunoglobulin A1 (IgA1) proteases is a characteristic of Haemophilus influenzae and several other bacterial pathogens causing infectious diseases, including meningitis. Indirect evidence suggests that the proteases are important virulence factors. In this study, we cloned the iga gene encoding immunoglob...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.57.10.3097-3105.1989

    authors: Poulsen K,Brandt J,Hjorth JP,Thøgersen HC,Kilian M

    更新日期:1989-10-01 00:00:00

  • In vivo behavior of revertants from Stahylococcus aureus L-phase variants compared with the parent strain.

    abstract::The in vivo behavior of revertants of Staphylococcus aureus L-phase variants were studied in mice. The Giorgio strain of S. aureus was induced into L-phase variants by methicillin. After 13 serial passages in methicillin agar and six passages in antibiotic-free agar, reversion occurred. Six revertants, all phage untyp...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.11.6.1182-1186.1975

    authors: Watanakunakorn C,Glotzbecker C

    更新日期:1975-06-01 00:00:00

  • Biochemical and biological characterization of the protective Leishmania pifanoi amastigote antigen P-8.

    abstract::The Leishmania pifanoi amastigote antigen P-8 has been previously shown to induce protective immunity in a murine model of cutaneous leishmaniasis (L. Soong, S. M. Duboise, P. Kima, and D. McMahon-Pratt, Infect. Immun. 63:3559-3566, 1995). As this antigen is of interest for further vaccine studies, the biochemical cha...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.69.11.6776-6784.2001

    authors: Colmenares M,Tiemeyer M,Kima P,McMahon-Pratt D

    更新日期:2001-11-01 00:00:00

  • Pyrophosphatase of the roundworm Ascaris suum plays an essential role in the worm's molting and development.

    abstract::Previous studies indicated that inorganic pyrophosphatase of Ascaris suum (AsPPase) plays an important role in larval survival in the host. Here we describe a precise role for AsPPase in larval molting and development and also describe the potential role of recombinant AsPPase (rAsPPase) in protective immunity to A. s...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.73.4.1995-2004.2005

    authors: Islam MK,Miyoshi T,Yamada M,Tsuji N

    更新日期:2005-04-01 00:00:00

  • Mutant of Bordetella pertussis which lacks ability to produce filamentous hemagglutinin.

    abstract::Mutant cultures that lacked the ability to produce filamentous hemagglutinin were obtained by UV irradiation of Bordetella pertussis strain 18-323. Various biological activities of these mutants were compared with those of the parent culture. It was found that the leukocytosis-promoting, histamine-sensitizing, and mou...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.35.3.1018-1023.1982

    authors: Watanabe M,Nakase Y

    更新日期:1982-03-01 00:00:00

  • Identification and characterization of the PutP proline permease that contributes to in vivo survival of Staphylococcus aureus in animal models.

    abstract::Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscesses, endocarditis, and other infectious syndromes. A signature-tagged mutagenesis (STM) system was adapted for use in studying the genes required for in vivo survival of S. aureus. An STM library was ultimately create...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.66.2.567-572.1998

    authors: Schwan WR,Coulter SN,Ng EY,Langhorne MH,Ritchie HD,Brody LL,Westbrock-Wadman S,Bayer AS,Folger KR,Stover CK

    更新日期:1998-02-01 00:00:00

  • Involvement of CD14 and toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae.

    abstract::Invasive fungal infections represent an increasing problem associated with high mortality. The present study was undertaken to identify leukocyte subsets that are activated by hyphal fragments in a whole-human-blood model, as well as to examine the involvement of CD14 and Toll-like receptors (TLRs) in activation of mo...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.69.4.2402-2406.2001

    authors: Wang JE,Warris A,Ellingsen EA,Jørgensen PF,Flo TH,Espevik T,Solberg R,Verweij PE,Aasen AO

    更新日期:2001-04-01 00:00:00

  • Effects of acquired resistance on infection with Eimeria falciformis var. Pragensis in mice.

    abstract::Mice immunized with infections of 500, 5,000, or 20,000 oocysts of E. falciformis var. pragensis were reinfected with 20,000 and 100,000 oocysts at 20 and 38 days, respectively, after the initial infection. After the first challenge infection, none of the immunized mice showed clinical signs of coccidiosis; a few mice...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.23.1.108-114.1979

    authors: Mesfin GM,Bellamy JE

    更新日期:1979-01-01 00:00:00

  • Murine aerosol challenge model of anthrax.

    abstract::The availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. The infection of rabbits and non-human primates with fully virulent Bacillus anthracis spores provides two excellent models of anthrax disease. However, the high cost of procuring a...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.01875-06

    authors: Loving CL,Kennett M,Lee GM,Grippe VK,Merkel TJ

    更新日期:2007-06-01 00:00:00

  • Direct binding of human NK cell natural cytotoxicity receptor NKp44 to the surfaces of mycobacteria and other bacteria.

    abstract::Our previous studies demonstrated that Mycobacterium bovis bacillus Calmette-Guérin (BCG) can directly interact with human NK cells and induce the proliferation, gamma interferon production, and cytotoxic activity of such cells without the need for accessory cells. Thus, the aim of the present study was to identify th...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00870-07

    authors: Esin S,Batoni G,Counoupas C,Stringaro A,Brancatisano FL,Colone M,Maisetta G,Florio W,Arancia G,Campa M

    更新日期:2008-04-01 00:00:00

  • Susceptibility to reinfection after a primary chlamydial genital infection is associated with a decrease of antigen-specific T cells in the genital tract.

    abstract::We tested the hypothesis that the intensity of specific antichlamydial T cell-mediated immunity in the genital tract of female guinea pigs infected intravaginally with the chlamydial agent of guinea pig inclusion conjunctivitis would determine the resistance or susceptibility to reinfection after a primary chlamydial ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.59.4.1346-1351.1991

    authors: Igietseme JU,Rank RG

    更新日期:1991-04-01 00:00:00

  • Partition of Salmonella typhimurium in a two-polymer acqueous phase system in relation to liability to phagocytosis.

    abstract::Analysis of the partition in a two-polymer phase system of Salmonella typhimurium R mutants with different susceptibility to phagocytosis distinguished between the mutants. Close to 80% of the R mutants least resistant to phagocytosis accumulated in the dextran-rich phase, whereas more phagocytosis-resistant mutants s...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.8.1.36-41.1973

    authors: Stendahl O,Tagesson C,Edebo M

    更新日期:1973-07-01 00:00:00

  • Distribution of dengue-2 antigens by electron immunocytochemistry.

    abstract::The distribution of dengue-2 antigens was studied in infected monkey kidney cells (LLC MK2) using an indirect, horseradish peroxidase-conjugated immunoglobulin technique. This procedure allowed both light and electron microscopic examination of serial-step sections of individual cells cut in a plane perpendicular to t...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.13.6.1699-1709.1976

    authors: Cardiff RD,Lund JK

    更新日期:1976-06-01 00:00:00

  • In vitro production of an extracellular protease by Legionella pneumophila.

    abstract::Extracellular protease activity was measured in liquid cultures of representative strains from six serotypes of Legionella pneumophila. A variety of substrates were degraded, including denatured casein, skim milk, gelatin, and hide powder azure, but not elastin. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.34.1.299-302.1981

    authors: Thompson MR,Miller RD,Iglewski BH

    更新日期:1981-10-01 00:00:00

  • Truncation of fibronectin-binding proteins in Staphylococcus aureus strain Newman leads to deficient adherence and host cell invasion due to loss of the cell wall anchor function.

    abstract::Staphylococcus aureus fibronectin-binding proteins (FnBPs) play a critical role in S. aureus pathogenesis. FnBPs mediate adhesion to fibronectin and invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, by fibronectin bridging to the host cell fibronectin receptor integrin (alpha(5))b...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.72.12.7155-7163.2004

    authors: Grundmeier M,Hussain M,Becker P,Heilmann C,Peters G,Sinha B

    更新日期:2004-12-01 00:00:00

  • Skin lesions produced by Staphylococcus aureus exfoliatin in hairless mice.

    abstract::Exfoliatin caused skin loss in hairless mutant mice only while they lacked hair, but older mice were more resistant to this effect than neonates. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.6.5.877-879.1972

    authors: Kapral FA,Miller MM

    更新日期:1972-11-01 00:00:00

  • Estimation of growth parameters for some oral bacteria grown in continuous culture under glucose-limiting conditions.

    abstract::The coexistence of bacteria in natural environments can often be explained in terms of competition for a growth-limiting substrate(s), and the outcome of such competition depends upon relevant growth parameters such as substrate affinity and yield. Dental plaque bacteria are frequently carbon and energy limited. Growt...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.52.3.897-901.1986

    authors: Rogers AH,de Jong MH,Zilm PS,van der Hoeven JS

    更新日期:1986-06-01 00:00:00

  • Eukaryotic cell uptake of heparin-coated microspheres: a model of host cell invasion by Chlamydia trachomatis.

    abstract::Using polystyrene microspheres coated with heparin or heparan sulfate, it was shown that coated microspheres specifically bound eukaryotic cells and were endocytosed by nonprofessional phagocytic cells. Coated microspheres displayed properties of binding to eukaryotic cells that were similar to those of chlamydiae, an...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.3.1080-1085.2000

    authors: Stephens RS,Fawaz FS,Kennedy KA,Koshiyama K,Nichols B,van Ooij C,Engel JN

    更新日期:2000-03-01 00:00:00

  • Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection.

    abstract::The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccine has not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scru...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00157-16

    authors: Raja AI,Cai Y,Reiman JM,Groves P,Chakravarty S,McPhun V,Doolan DL,Cockburn I,Hoffman SL,Stanisic DI,Good MF

    更新日期:2016-07-21 00:00:00

  • Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice.

    abstract::Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understan...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.02790-14

    authors: de Souza Filho JA,de Paulo Martins V,Campos PC,Alves-Silva J,Santos NV,de Oliveira FS,Menezes GB,Azevedo V,Cravero SL,Oliveira SC

    更新日期:2015-04-01 00:00:00

  • Micronemal transport of Plasmodium ookinete chitinases to the electron-dense area of the apical complex for extracellular secretion.

    abstract::Plasmodium ookinetes secrete chitinases to penetrate the acellular, chitin-containing peritrophic matrix of the mosquito midgut en route to invasion of the epithelium. Chitinases are potentially targets that can be used to block malaria transmission. We demonstrate here that chitinases of Plasmodium falciparum and P. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.11.6461-6465.2000

    authors: Langer RC,Hayward RE,Tsuboi T,Tachibana M,Torii M,Vinetz JM

    更新日期:2000-11-01 00:00:00