Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment.

Abstract:

:The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe. The surface of the C-terminal fragment of outer surface protein A (OspA) was divided into distinct regions, based primarily on binding sites of monoclonal antibodies (MAbs). In order to target the six clinically most relevant OspA serotypes (ST) in a single protein, exposed amino acids of the individual regions were exchanged to corresponding amino acids of a chosen OspA serotype. Six chimeric proteins were constructed, and, based on their immunogenicity, four of these chimeras were tested in mouse challenge models. Significant protection could be demonstrated for all four proteins following challenge with infected ticks (OspA ST1, OspA ST2, and OspA ST4) or with in vitro-grown spirochetes (OspA ST1 and OspA ST5). Two of the chimeric proteins were linked to form a fusion protein, which provided significant protection against in vitro-grown spirochetes (OspA ST1) and infected ticks (OspA ST2). This article presents the proof-of-concept study for a multivalent OspA vaccine targeting a wide range of pathogenic LB Borrelia species with a single recombinant antigen for prevention of Lyme borreliosis.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Nayak A,Schüler W,Seidel S,Gomez I,Meinke A,Comstedt P,Lundberg U

doi

10.1128/IAI.00917-19

subject

Has Abstract

pub_date

2020-03-23 00:00:00

issue

4

eissn

0019-9567

issn

1098-5522

pii

IAI.00917-19

journal_volume

88

pub_type

杂志文章
  • Putative β-Barrel Outer Membrane Proteins of the Bovine Digital Dermatitis-Associated Treponemes: Identification, Functional Characterization, and Immunogenicity.

    abstract::Bovine digital dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal etiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently soug...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00050-20

    authors: Staton GJ,Carter SD,Ainsworth S,Mullin J,Smith RF,Evans NJ

    更新日期:2020-04-20 00:00:00

  • Antibody response to a Babesia bigemina rhoptry-associated protein 1 surface-exposed and neutralization-sensitive epitope in immune cattle.

    abstract::Protective immunity against Babesia bigemina is hypothesized to involve antibodies directed against merozoite surface-exposed epitopes. Levels of antibody against a rhoptry-associated protein 1 (RAP-1) B-lymphocyte epitope, defined by surface-reactive and inhibitory monoclonal antibodies, in immune cattle sera were de...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.12.5698-5701.1994

    authors: Ushe TC,Palmer GH,Sotomayor L,Figueroa JV,Buening GM,Perryman LE,McElwain TF

    更新日期:1994-12-01 00:00:00

  • Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection.

    abstract::Mucosa-associated invariant T (MAIT) cells are an innate-like T cell subset in mammals that recognize microbial vitamin B metabolites presented by the evolutionarily conserved major histocompatibility complex class I (MHC I)-related molecule, MR1. Emerging data suggest that MAIT cells may be an attractive target for v...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00524-20

    authors: Vorkas CK,Levy O,Skular M,Li K,Aubé J,Glickman MS

    更新日期:2020-12-15 00:00:00

  • Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.

    abstract::Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white l...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.55.1.16-23.1987

    authors: Stimpson SA,Lerch RA,Cleland DR,Yarnall DP,Clark RL,Cromartie WJ,Schwab JH

    更新日期:1987-01-01 00:00:00

  • Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand.

    abstract::A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasin...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.8.3564-3567.1994

    authors: Appelmelk BJ,An YQ,Thijs BG,MacLaren DM,de Graaff J

    更新日期:1994-08-01 00:00:00

  • Activity and specificity of a mouse monoclonal antibody to ferric aerobactin.

    abstract::We isolated a monoclonal antibody directed against the ferric complex of aerobactin purified from Escherichia coli KH576. This antibody, which we designated MAb AERO1, was identified as an immunoglobulin G, subtype 2. A competitive enzyme-linked immunosorbent assay with MAb AERO1 had a limit of 10 nM for the detection...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.60.3.768-772.1992

    authors: le Roy D,Expert D,Razafindratsita A,Deroussent A,Cosme J,Bohuon C,Andremont A

    更新日期:1992-03-01 00:00:00

  • Infection of multiple T-cell subsets and changes in lymphocyte functions associated with Herpesvirus saimiri infection of owl monkeys.

    abstract::We examined the association of Herpesvirus saimiri with lymphocyte subsets and the functional integrity and distribution of these populations in owl monkeys with chronic, disease-free infections, in uninoculated, control animals, and in one monkey with H. saimiri-induced lymphoma. The lymphocyte subpopulations examine...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.32.2.698-706.1981

    authors: Neubauer RH,Dunn FE,Rabin H

    更新日期:1981-05-01 00:00:00

  • Inhibition of translocation of viable Escherichia coli from the gastrointestinal tract of mice by bacterial antagonism.

    abstract::The incidence of translocation of viable Escherichia coli C25 from the gastrointestinal tract to the mesenteric lymph nodes was compared in gnotobiotic mice colonized with only E. coli C25 and in gnotobiotic mice colonized with E. coli C25 plus the whole cecal flora from specific pathogen-free mice. The population lev...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.25.3.820-827.1979

    authors: Berg RD,Owens WE

    更新日期:1979-09-01 00:00:00

  • Type C virus and immunoglobulin A production by murine myeloma MOPC-315: two independent activities.

    abstract::The suspected correlation between cessation of type C virus production and halt in immunoglobulin secretion by murine myeloma cells was studied. Employing two variants of the murine myeloma MOPC-315, immunoglobulin A-producing and nonproducing cells, we demonstrated that the two myelomas release similar levels of type...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.25.2.569-573.1979

    authors: Gazit A,Yaniv A,Halperin D,Ben-Efraim S

    更新日期:1979-08-01 00:00:00

  • Production and characterization of monoclonal antibodies against Clostridium perfringens type A enterotoxin.

    abstract::Hybridomas secreting monoclonal antibodies (MABs) specific for Clostridium perfringens type A enterotoxin were produced by fusion of P3X63Ag8.653 myeloma cells with spleen cells from BALB/c mice immunized with purified enterotoxin. Wells containing hybridomas secreting immunoglobulin G (IgG) antibodies against enterot...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.50.2.442-448.1985

    authors: Wnek AP,Strouse RJ,McClane BA

    更新日期:1985-11-01 00:00:00

  • Molecular approach to the epidemiology of swine vesicular disease: correlation of variation in the virus structural polypeptides with serological properties.

    abstract::Variation has been observed in the structural polypeptides of swine vesicular disease viruses isolated from the United Kingdom and Hong Kong. Despite the limited number of isolates examined, several distinct polypeptide patterns were obtained when the virus structural proteins were examined by polyacrylamide gel elect...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.24.3.593-599.1979

    authors: Harris TJ,Underwood BO,Knowles NJ,Crowther JR,Brown F

    更新日期:1979-06-01 00:00:00

  • Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection.

    abstract::Pseudomonas aeruginosa utilizes a number of distinct pathways to secrete proteins that play various roles during infection. These include the type II secretion system, which is responsible for the secretion of the majority of exoproducts into the surrounding environment, including toxins and degradative enzymes. In co...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.73.3.1695-1705.2005

    authors: Lee VT,Smith RS,Tümmler B,Lory S

    更新日期:2005-03-01 00:00:00

  • Infection with Chlamydia trachomatis alters the tyrosine phosphorylation and/or localization of several host cell proteins including cortactin.

    abstract::Infection of epithelial cells by two biovars of Chlamydia trachomatis results in the tyrosine phosphorylation of several host proteins. The most prominent change in host protein tyrosine phosphorylation involves a complex of proteins with molecular masses of 75 to 85 kDa (pp75/85) and 100 kDa (pp100). The C. trachomat...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.65.12.5301-5308.1997

    authors: Fawaz FS,van Ooij C,Homola E,Mutka SC,Engel JN

    更新日期:1997-12-01 00:00:00

  • Influence of the bursa of Fabricius on the pathogenesis of Marek's disease.

    abstract::A series of experiments was conducted to study the influence of embryonal bursectomy (EBX) on the early and late pathogenesis of Marek's disease (MD). The early lytic infection in the lymphoid organs normally associated with oncogenic MD virus infection in intact chickens was not seen in EBX chickens. Therefore, the d...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.31.1.199-207.1981

    authors: Schat KA,Calnek BW,Fabricant J

    更新日期:1981-01-01 00:00:00

  • Blockade of costimulation prevents infection-induced immunopathology in interleukin-10-deficient mice.

    abstract::Interleukin-10 (IL-10) is associated with inhibition of cell-mediated immunity and downregulation of the expression of costimulatory molecules required for T-cell activation. When IL-10-deficient (IL-10KO) mice are infected with Toxoplasma gondii, they succumb to a T-cell-mediated shock-like reaction characterized by ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.5.2837-2844.2000

    authors: Villegas EN,Wille U,Craig L,Linsley PS,Rennick DM,Peach R,Hunter CA

    更新日期:2000-05-01 00:00:00

  • Methylthioadenosine Suppresses Salmonella Virulence.

    abstract::In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously, we showed a transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) concentration in serum during systemic Salmonella enterica serovar T...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00429-18

    authors: Bourgeois JS,Zhou D,Thurston TLM,Gilchrist JJ,Ko DC

    更新日期:2018-08-22 00:00:00

  • Burkholderia cenocepacia ShvR-regulated genes that influence colony morphology, biofilm formation, and virulence.

    abstract::Burkholderia cenocepacia is an opportunistic pathogen that primarily infects cystic fibrosis (CF) patients. Previously, we reported that ShvR, a LysR regulator, influences colony morphology, virulence, and biofilm formation and regulates the expression of an adjacent 24-kb genomic region encoding 24 genes. In this stu...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00170-11

    authors: Subramoni S,Nguyen DT,Sokol PA

    更新日期:2011-08-01 00:00:00

  • The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides.

    abstract::The actions of polymyxin B, rabbit polymorphonuclear lysosome extracts, 14 polycationic peptides (including defensin NP-2, cecropin P1, lactoferricin B, and active peptides from cationic protein 18 and bactenecin), EDTA, and Tris on Brucella spp. were studied, with other gram-negative bacteria as controls. Brucella sp...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.63.8.3054-3061.1995

    authors: Martínez de Tejada G,Pizarro-Cerdá J,Moreno E,Moriyón I

    更新日期:1995-08-01 00:00:00

  • Induction and expression of cell-mediated immune responses in inbred mice infected with Coccidioides immitis.

    abstract::Comparisons of the course of coccidioidomycosis in two strains of inbred mice established that BALB/c mice are significantly more susceptible to pulmonary infection with Coccidioides immitis than are DBA/2 mice. The susceptibility of BALB/c mice does not reside in their inability to mount a delayed-type hypersensitivi...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.1.13-17.1988

    authors: Cox RA,Kennell W,Boncyk L,Murphy JW

    更新日期:1988-01-01 00:00:00

  • Predominant gram-positive bacteria in human feces: numbers, variety, and persistence.

    abstract::The predominant gram-positive bacteria in 47 fecal specimens from 10 healthy men were studied by microscopic and cultural counts, by the characterization and tentative identification of isolates, and by the use of fluorescein isothiocyanate (FITC)-conjugated globulins prepared using some of the isolates. Gram-positive...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.9.4.719-729.1974

    authors: Gossling J,Slack JM

    更新日期:1974-04-01 00:00:00

  • Potentiating effect of bile on enterotoxin-induced diarrhea.

    abstract::The influence of bile acids on adenosine 3',5'-phosphate-induced intestinal secretion was studied in mice. Bile flow was stopped by ligation of the common bile duct, and secretion was induced in ligated loops of the small intestine. The decrease of bile led to inhibition of hypersecretion after challenge with heat-lab...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.35.2.391-395.1982

    authors: Lange S,Lönnroth I

    更新日期:1982-02-01 00:00:00

  • Novel adjuvant action of lipopolysaccharides that possess mannose homopolysaccharides as O-specific polysaccharides on immune responses to nonimmunogenic autoantigens in mice.

    abstract::The adjuvant action of various lipopolysaccharides on immune responses to syngeneic tissue extract in mice was examined. Only lipopolysaccharides possessing the linear mannose homopolysaccharides as O-specific polysaccharides exhibited definite adjuvant action on immune responses to the autoantigens. The intensity of ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.60.11.4953-4956.1992

    authors: Yokochi T,Fukada M,Kawai M,Zhang YH,Jiang GZ,Takahashi K

    更新日期:1992-11-01 00:00:00

  • Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus.

    abstract::The virulence and fitness in vivo of the major human pathogen Staphylococcus aureus are associated with a cell-to-cell signaling mechanism known as quorum sensing (QS). QS coordinates the production of virulence factors via the production and sensing of autoinducing peptide (AIP) signal molecules by the agr locus. Her...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.01216-13

    authors: Pollitt EJ,West SA,Crusz SA,Burton-Chellew MN,Diggle SP

    更新日期:2014-03-01 00:00:00

  • Purification and characterization of a high-molecular-weight outer membrane protein of Moraxella (Branhamella) catarrhalis.

    abstract::Moraxella (Branhamella) catarrhalis is an important bacterial cause of otitis media in children and lower respiratory tract infections in adults. In this study, we describe the presence of a novel high-molecular-weight outer membrane protein (HMW-OMP). This protein varies from 350 to 720 kDa in apparent molecular mass...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.4.1150-1155.1994

    authors: Klingman KL,Murphy TF

    更新日期:1994-04-01 00:00:00

  • Innate immune response to Streptococcus iniae infection in zebrafish larvae.

    abstract::Streptococcus iniae causes systemic infection characterized by meningitis and sepsis. Here, we report a larval zebrafish model of S. iniae infection. Injection of wild-type S. iniae into the otic vesicle induced a lethal infection by 24 h postinfection. In contrast, an S. iniae mutant deficient in polysaccharide capsu...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00642-12

    authors: Harvie EA,Green JM,Neely MN,Huttenlocher A

    更新日期:2013-01-01 00:00:00

  • Macrophage activation during experimental murine brucellosis: a basis for chronic infection.

    abstract::Evidence is presented that the chronicity of infection in CBA mice after injection of Brucella abortus 19 is related to a number of factors: (i) the relative resistance of B. abortus to macrophage killing, which allowed some bacteria to survive the peak of macrophage activity occurring at 14 days; (ii) the decline in ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.23.2.197-205.1979

    authors: Cheers C,Pagram F

    更新日期:1979-02-01 00:00:00

  • Analysis of Escherichia coli strains causing bacteriuria during pregnancy: selection for strains that do not express type 1 fimbriae.

    abstract::Escherichia coli isolates from patients with bacteriuria of pregnancy were compared by PCR with isolates from patients with community-acquired cystitis for the presence of established virulence determinants. The strains from patients with bacteriuria of pregnancy were less likely to carry genes for P-family, S-family,...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.69.2.794-799.2001

    authors: Graham JC,Leathart JB,Keegan SJ,Pearson J,Bint A,Gally DL

    更新日期:2001-02-01 00:00:00

  • Immunoglobulin-binding activity among pathogenic and carrier isolates of Haemophilus somnus.

    abstract::Nonimmune binding of immunoglobulin to whole bacteria was quantitated for North American isolates of Haemophilus somnus recovered from cattle with pneumonia, reproductive failure (abortion), or thromboembolic meningoencephalitis or from the vagina or prepuce of carrier cattle. Quantitative binding activity covered a w...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.57.2.639-642.1989

    authors: Widders PR,Dorrance LA,Yarnall M,Corbeil LB

    更新日期:1989-02-01 00:00:00

  • Effects of complement depletion in experimental chagas disease: immune lysis of virulent blood forms of Trypanosoma cruzi.

    abstract::In mice infected with virulent blood (trypomastigote) forms of Trypanosoma cruzi, complement depletion with cobra venom factor caused a marked exacerbation of the disease evidenced by significantly increased parasitemia levels and early mortality as compared with those of untreated infected animals. The effect was gre...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.11.1.86-91.1975

    authors: Budzko DB,Pizzimenti MC,Kierszenbaum F

    更新日期:1975-01-01 00:00:00

  • Lymphocyte function-associated antigen 1 is a receptor for Pasteurella haemolytica leukotoxin in bovine leukocytes.

    abstract::Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate that P. haemolytica Lkt binds to bovine CD18, the common subunit of all beta2 integrins. We designed experiments with the following objectives: to identify which member o...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.1.72-79.2000

    authors: Jeyaseelan S,Hsuan SL,Kannan MS,Walcheck B,Wang JF,Kehrli ME,Lally ET,Sieck GC,Maheswaran SK

    更新日期:2000-01-01 00:00:00