East Setauket, NY, United States
East Setauket, NY, United States

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Lahey L.J.,Geriatric Research Education and Clinical Center | Lahey L.J.,Stanford University | Panas M.W.,Stanford University | Mao R.,Geriatric Research Education and Clinical Center | And 15 more authors.
Journal of Clinical Microbiology | Year: 2015

The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P<0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. © 2015, American Society for Microbiology.


Arnaboldi P.M.,Biopeptides Corporation | Arnaboldi P.M.,New York Medical College | Seedarnee R.,New York Medical College | Sambir M.,Biopeptides Corporation | And 4 more authors.
Clinical and Vaccine Immunology | Year: 2013

Current serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are crossreactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific for Borrelia burgdorferi as diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor of B. burgdorferi required for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-aminoacid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection. © 2013, American Society for Microbiology. All Rights Reserved.


Arnaboldi P.M.,Biopeptides Corporation | Arnaboldi P.M.,New York Medical College | Dattwyler R.J.,Biopeptides Corporation | Dattwyler R.J.,New York Medical College
Clinical and Vaccine Immunology | Year: 2015

Epitope mapping of the p66 outer membrane protein of Borrelia burgdorferi revealed that the protein contains numerous crossreactive linear epitopes recognized by serum antibody in the majority of individuals tested, regardless of Lyme disease history, limiting the usefulness of this antigen in Lyme disease serodiagnostic assays.


Signorino G.,New York Medical College | Signorino G.,Messina University | Arnaboldi P.M.,New York Medical College | Arnaboldi P.M.,Biopeptides Corporation | And 3 more authors.
Clinical and Vaccine Immunology | Year: 2014

Laboratory diagnosis of Lyme disease is based on the serological detection of antibodies against the etiologic agent Borrelia burgdorferi. Current diagnostics are insensitive at detecting early infection, when treatment is most effective. This deficiency results from the limited number of B. burgdorferi antigens expressed in early infection and the use of an insensitive two-tier paradigm, put in place to deal with insufficient specificity associated with the use of whole-protein antigens and/or bacterial lysates as serodiagnostic targets. Whole-protein antigens contain epitopes that are unique to B. burgdorferi as well as cross-reactive epitopes found in other bacteria. One method for overcoming the limitations imposed by cross-reactive epitopes is the use of short peptides containing epitopes unique to B. burgdorferi as antigen targets. This eliminates nonspecific epitopes. Using overlapping peptide libraries, we performed epitope mapping of linear epitopes in oligopeptide permease A2 (OppA2), a member of the oligopeptide permease (Opp) family of peptide transporters, expressed during early B. burgdorferi infection. We identified 9 epitopes, synthesized peptides containing these epitopes, and screened those using panels of blood from patients with early Lyme disease, rheumatoid arthritis (RA), or syphilis or from healthy individuals. Two of the peptides, OppA2 (191-225) (amino acids comprising the peptide are shown in parentheses) and OppA2 (381-400), are highly conserved among the three major pathogenic Borrelia species responsible for most Lyme disease cases in North America and Europe. They detected antibodies in Lyme disease patient sera with sufficient sensitivity and specificity to indicate that they could have value in a serological assay for Lyme disease. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Arnaboldi P.M.,Biopeptides Corporation | Arnaboldi P.M.,New York Medical College | Sambir M.,Biopeptides Corporation | Sambir M.,New York Medical College | And 2 more authors.
Clinical and Vaccine Immunology | Year: 2014

The laboratory diagnosis of Lyme disease is based upon the detection of antibodies generated against Borrelia burgdorferi using a two-tier assay, typically consisting of an enzyme-linked immunosorbent assay (ELISA), followed by a Western blot. This system, put into place to address the nonspecificity associated with standalone first-tier assays, is insensitive for diagnosing early infection, when most people seek care. The use of bacterial lysates or whole-protein antigens as first-tier assay targets contributes to nonspecificity due, in part, to the presence of cross-reactive epitopes that are also found in other bacteria. This precludes their use as sensitive standalone assays. The use of peptides containing linear epitopes that are highly specific for B. burgdorferi offers a method for reducing this cross-reactivity. In the present study, we mapped the linear epitopes of the prominently expressed Borrelia adhesins decorin binding protein A (DbpA) and DbpB. We identified several epitopes in each protein that were highly conserved among North American strains of B. burgdorferi, and we screened peptides containing specific epitopes using serum panels from early and late Lyme disease patients. The individual peptides primarily detected IgM but not IgG, while the proteins efficiently detected both IgM and IgG. While no individual peptide demonstrated better utility for antibody detection than its respective whole protein, an assay containing a combination of a DbpA and a DbpB peptide adequately detected both IgM and IgG, accurately identifying 87.5% (84/96) of the early Lyme disease patients and 80.0% (16/20) of the late Lyme disease patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Lourdault K.,VA Greater Los Angeles Healthcare System | Lourdault K.,University of California at Los Angeles | Wang L.-C.,VA Greater Los Angeles Healthcare System | Vieira A.,University of Tennessee Health Science Center | And 7 more authors.
Infection and Immunity | Year: 2014

Leptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine. Leptospira interrogans serovar Copenhageni transmitted from Rattus norvegicus to humans is the most prevalent cause of urban leptospirosis. We examined L. interrogans LigA, domains 7 to 13 (LigA7-13), as an oral vaccine delivered by Escherichia coli as a lipidated, membrane-associated protein. The efficacy of the vaccine was evaluated in a susceptible hamster model in terms of the humoral immune response and survival from leptospiral challenge. Four weeks of oral administration of live E. coli expressing LigA7-13 improved survival from intraperitoneal (i.p.) and intradermal (i.d.) challenge by L. interrogans serovar Copenhageni strain Fiocruz L1-130 in Golden Syrian hamsters. Immunization with E. coli expressing LigA7-13 resulted in a systemic antibody response, and a significant LigA7-13 IgG level after the first 2 weeks of immunization was completely predictive of survival 28 days after challenge. As in previous LigA vaccine studies, all immunized hamsters that survived infection had renal leptospiral colonization and histopathological changes. In summary, an oral LigA-based vaccine improved survival from leptospiral challenge by either the i.p. or i.d. route. © 2014, American Society for Microbiology.


del Rio B.,University of Tennessee Health Science Center | Seegers J.F.M.L.,Lactrys Biopharmaceuticals BV | Gomes-Solecki M.,University of Tennessee Health Science Center | Gomes-Solecki M.,Biopeptides Corporation
PLoS ONE | Year: 2010

Background: Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response. Methodology/Principal Findings: We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively. Conclusions/Significance: Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response. © 2010 del Rio et al.


Richer L.M.,University of Tennessee Health Science Center | Aroso M.,Biopeptides Corporation | Contente-Cuomo T.,Biopeptides Corporation | Ivanova L.,University of Tennessee Health Science Center | And 2 more authors.
Clinical and Vaccine Immunology | Year: 2011

Lyme disease is caused by the spirochete Borrelia burgdorferi. The enzootic cycle of this pathogen requires that Ixodes spp. acquire B. burgdorferi from infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to control B. burgdorferi; there is no human vaccine available, and existing vector control measures are generally not acceptable to the public. However, if B. burgdorferi could be eliminated from its reservoir hosts or from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. We developed OspA-RTV, a reservoir targeted bait vaccine (RTV) based on the immunogenic outer surface protein A (OspA) of B. burgdorferi aimed at breaking the natural cycle of this spirochete. White-footed mice, the major reservoir species for this spirochete in nature developed a systemic OspA-specific IgG response as a result of ingestion of the bait formulation. This immune response protected white-footed mice against B. burgdorferi infection upon tick challenge and cleared B. burgdorferi from the tick vector. In performing extensive studies to optimize the OspA-RTV for field deployment, we determined that mice that consumed the vaccine over periods of 1 or 4 months developed a yearlong, neutralizing anti-OspA systemic IgG response. Furthermore, we defined the minimum number of OspA-RTV units needed to induce a protective immune response. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Patent
Biopeptides Corporation | Date: 2013-02-01

The present invention relates, e.g., to a composition comprising peptides represented by SEQ ID NO:1-SEQ ID NO:28 and/or SEQ ID NO:41-SEQ ID NO:47, or active variants thereof, wherein the peptides or active variants can bind specifically to an antibody induced by a causative agent of Lyme disease (a pathogenic Borrelia), e.g. in a sample from a subject having Lyme disease. Compositions of the invention may comprise multiple peptides, from multiple proteins. Diagnostic kits comprising the peptides are described, as are diagnostic assays using the peptides.


Patent
BIOPEPTIDES Corporation | Date: 2014-12-08

The present invention relates, e.g., to a composition comprising peptides represented by SEQ ID NO:1, or active variants thereof, wherein the peptides or active variants can bind specifically to an antibody induced by a causative agent of Lyme disease (a pathogenic Borrelia), e.g. in a sample from a subject having Lyme disease. Compositions of the invention may comprise multiple peptides, from multiple proteins. Diagnostic kits comprising the peptides are described, as are diagnostic assays using the peptides.

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