Chimeric OspA genes, proteins and methods of use thereof

Title: Chimeric OspA genes, proteins and methods of use thereof

Abstract

The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.

Inventors:: Crowe, Brian A.; Livey, Ian; O'Rourke, Maria; Schwendinger, Michael; Dunn, John J.; Luft, Benjamin J.

Issue Date:: 2018-02-20

Research Org.:: Research Foundation of the State University of New York, Amherst, NY; Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1422826

Patent Number(s):: 9895434

Application Number:: 15/049,438

Assignee:: Brookhaven Science Associates, LLC (Upton, NY)

Patent Classifications (CPCs):: A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

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A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K39/0225 - {Spirochetes, e.g. Treponema, Leptospira, Borrelia}
A61K2039/575 - {humoral response}

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P33/14 - Ectoparasiticides, e.g. scabicides
A61P31/04 - Antibacterial agents
A61P33/00 - Antiparasitic agents

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K2039/6018 - {Lipids, e.g. in lipopeptides}

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
C07K14/20 - from Spirochaetales

Y - NEW / CROSS SECTIONAL TECHNOLOGIES Y02 - TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE Y02A - TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
Y02A50/30 - Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P43/00 - Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
A61P31/14 - for RNA viruses
A61P31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A61K2039/70 - {Multivalent vaccine}

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P37/04 - Immunostimulants

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DOE Contract Number:: DE-SC0012704

Resource Type:: Patent

Resource Relation:: Patent File Date: 2016 Feb 22

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES

Citation Formats


                    Crowe, Brian A., Livey, Ian, O'Rourke, Maria, Schwendinger, Michael, Dunn, John J., and Luft, Benjamin J. Chimeric OspA genes, proteins and methods of use thereof.  United States: N. p., 2018. 
        Web.

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                    Crowe, Brian A., Livey, Ian, O'Rourke, Maria, Schwendinger, Michael, Dunn, John J., & Luft, Benjamin J. Chimeric OspA genes, proteins and methods of use thereof.  United States.

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                    Crowe, Brian A., Livey, Ian, O'Rourke, Maria, Schwendinger, Michael, Dunn, John J., and Luft, Benjamin J. Tue .  
        "Chimeric OspA genes, proteins and methods of use thereof".  United States.  https://www.osti.gov/servlets/purl/1422826.

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@article{osti_1422826,

  title        = {Chimeric OspA genes, proteins and methods of use thereof},

  author       = {Crowe, Brian A. and Livey, Ian and O'Rourke, Maria and Schwendinger, Michael and Dunn, John J. and Luft, Benjamin J.},

  abstractNote = {The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.},

  doi          = {},

  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {2018},

  month        = {2}

}

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US Patent Document 4,179,337
URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F4179337

Replacing the complementarity-determining regions in a human antibody with those from a mouse
journal, May 1986

Jones, Peter T.; Dear, Paul H.; Foote, Jefferson
Nature, Vol. 321, Issue 6069, p. 522-525
https://doi.org/10.1038/321522a0

Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults
journal, December 1996

Van Hoecke, C.; Comberbach, M.; De Grave, D.
Vaccine, Vol. 14, Issue 17-18, p. 1620-1626
https://doi.org/10.1016/S0264-410X(96)00146-6

Expression of tetanus toxin fragment C in E.coli : high level expression by removing rare codons
journal, January 1989

Makoff, A. J.; Oxer, M. D.; Romanos, M. A.
Nucleic Acids Research, Vol. 17, Issue 24, p. 10191-10202
https://doi.org/10.1093/nar/17.24.10191

Immunometric assays using monoclonal antibodies
patent, March 1983

David, Gary S.; Greene, Howard E.
US Patent Document 4,376,110
URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F4376110

Humanized immunoglobulins
patent, December 1997

Queen, Cary L.; Co, Man Sung; Schneider, William P.
US Patent Document 5,693,762
URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F5693762

Structural identification of a key protective B-cell epitope in lyme disease antigen OspA
journal, October 2000

Ding, Wei; Huang, Xiaolin; Yang, Xiaohua
Journal of Molecular Biology, Vol. 302, Issue 5, p. 1153-1164
https://doi.org/10.1006/jmbi.2000.4119

Abilities of OspA proteins from different seroprotective groups of Borrelia burgdorferi to protect hamsters from infection.
journal, January 1995

Lovrich, S. D.; Callister, S. M.; DuChateau, B. K.
Infection and immunity, Vol. 63, Issue 6
https://doi.org/10.1128/IAI.63.6.2113-2119.1995

SV40 DNA transfection of cells in suspension: analysis of the efficiency of transcription and translation of T-antigen
journal, March 1981

Chu, Gilbert; Sharp, Phillip A.
Gene, Vol. 13, Issue 2, p. 197-202
https://doi.org/10.1016/0378-1119(81)90008-1

Inhibition of Borrelia burgdorferi-Tick Interactions In Vivo by Outer Surface Protein A Antibody
journal, June 2001

Pal, U.; Montgomery, R. R.; Lusitani, D.
The Journal of Immunology, Vol. 166, Issue 12, p. 7398-7403
https://doi.org/10.4049/jimmunol.166.12.7398

A comprehensive set of sequence analysis programs for the VAX
journal, January 1984

Devereux, John; Haeberli, Paul; Smithies, Oliver
Nucleic Acids Research, Vol. 12, Issue 1, p. 387-395
https://doi.org/10.1093/nar/12.1Part1.387

Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi sensu stricto and Borrelia afzelii strains but reveals major subgroups within the Borrelia garinii species
journal, August 1995

Will, G.; Jauris-Heipke, S.; Schwab, E.
Medical Microbiology and Immunology, Vol. 184, Issue 2, p. 73-80
https://doi.org/10.1007/BF00221390

Immunization with a polyvalent OspA vaccine protects mice against Ixodes ricinus tick bites infected by Borrelia burgdorferi ss, Borrelia garinii and Borrelia afzelii
journal, October 1997

Gern, Lise; Hu, Chang Min; Voet, Pierre
Vaccine, Vol. 15, Issue 14, p. 1551-1557
https://doi.org/10.1016/S0264-410X(97)00066-2

Amino acid substitution matrices from protein blocks.
journal, November 1992

Henikoff, S.; Henikoff, J. G.
Proceedings of the National Academy of Sciences, Vol. 89, Issue 22, p. 10915-10919
https://doi.org/10.1073/pnas.89.22.10915

Chimeric proteins comprising borrelia polypeptides and uses therefor
patent, June 2001

Dunn, John J.; Luft, Benjamin J.
US Patent Document 6,248,562
URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F6248562

Applications and statistics for multiple high-scoring segments in molecular sequences.
journal, June 1993

Karlin, S.; Altschul, S. F.
Proceedings of the National Academy of Sciences, Vol. 90, Issue 12, p. 5873-5877
https://doi.org/10.1073/pnas.90.12.5873

Humanized immunoglobulins
patent, December 1996

Queen, Cary L.; Selick, Harold E.
US Patent Document 5,585,089
URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F5585089

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Similar Records

Title: Chimeric OspA genes, proteins and methods of use thereof

Abstract

Citation Formats

Osp a proteins of Borrelia burgdorferi subgroups, encoding genes and vaccines patent, January 2004

Gene Synthesis[New Synthetic Methods(77)] journal, June 1989

Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab journal, April 1997

Reshaping human antibodies: grafting an antilysozyme activity journal, March 1988

Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi journal, April 1989

Recombinant constructs of Borrelia burgdorferi patent, March 2006

Structure-based Design of a Second-generation Lyme Disease Vaccine Based on a C-terminal Fragment of Borrelia burgdorferi OspA journal, July 2005

[14] Protein biotinylation book, January 1990

Novel pharmaceutically active N-(2-aminoacylamido-2-deoxy-hexosyl)-amides, -carbamates and -ureas patent, August 1989

Effects of amino acid sequence changes on antibody-antigen interactions journal, January 1994

Borrelia antigen patent, November 1997

Method of making a projection viewable transparency comprising an electrostatographic toner image patent, August 1993

Use of deoxyinosine-containing primers vs degenerate primers for polymerase chain reaction based on ambiguous sequence information journal, April 1994

Identification of LFA-1 as a Candidate Autoantigen in Treatment-Resistant Lyme Arthritis journal, July 1998

Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes journal, May 1986

Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor journal, August 2000

Genetic Analysis of Protein Stability and Function journal, December 1989

Analysis of the Lipidated Recombinant Outer Surface Protein A fromBorrelia burgdorferiby Mass Spectrometry journal, March 1997

Enhanced Production of Recombinant Mycobacterium tuberculosis Antigens in Escherichia coli by Replacement of Low-Usage Codons journal, January 2000

Using Codon Usage to Predict Genes Origin: Is the Escherichia coli Outer Membrane a Patchwork of Products from Different Genomes? journal, January 1997

From genes to protein structure and function: novel applications of computational approaches in the genomic era journal, January 2000

Antibodies that react with predetermined sites on proteins journal, February 1983

Immunological adjuvant and process for preparing the same, pharmaceutical compositions, and process patent, October 1989

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery journal, April 1993

Improved tools for biological sequence comparison. journal, April 1988

Borrelia antigen patent, July 2000

Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. journal, September 1979

Strategies for Delivery of Peptides Utilizing Absorption-Enhancing Agents journal, December 1996

Recombinant immunoglobin preparations patent, March 1989

Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA. journal, January 1993

An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. journal, January 1993

Compositions and methods for administering Borrelia burgdorferi antigens patent, August 2006

Enhanced evolutionary PCR using oligonucleotides with inosine at the 3′-terminus journal, January 1991

A new technique for the assay of infectivity of human adenovirus 5 DNA journal, April 1973

Safety and Immunogenicity of a Recombinant Outer Surface Protein A Lyme Vaccine journal, June 1994

Purification of Borrelia burgdorferi outer surface protein A (OspA) and analysis of antibody binding domains. journal, January 1994

Reactivity with a specific epitope of outer surface protein A predicts protection from infection with the Lyme disease spirochete, Borrelia burgdorferi. journal, January 1997

Borrelia burdorferi Osp A and B proteins and immunogenic peptides patent, November 2000

Altered ospa of borrelia burgdorferi patent-application, December 2009

By-passing immunisation journal, September 1992

Reshaping human antibodies for therapy journal, March 1988

Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. journal, November 1984

Approaches toward the Directed Design of a Vaccine against Borrelia burgdorferi journal, February 2002

A Vaccine Consisting of Recombinant Borrelia burgdorferi Outer-Surface Protein A to Prevent Lyme Disease journal, July 1998

Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant journal, July 1998

By-passing immunization: Human antibodies from V-gene libraries displayed on phage journal, December 1991

Continuous cultures of fused cells secreting antibody of predefined specificity journal, August 1975

Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide journal, July 1963

Preparation and use of polyethylene glycol propionaldehyde patent, October 1993

Basic local alignment search tool journal, October 1990

Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. journal, January 1996

A general method applicable to the search for similarities in the amino acid sequence of two proteins journal, March 1970

OspA DNA and lyme disease vaccine patent, February 2001

Comparison of biosequences journal, December 1981

Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs journal, April 1990

The Lyme disease vaccine candidate outer surface protein A (OspA) in a formulation compatible with human use protects mice against natural tick transmission of B. burgdorferi journal, January 1995

Borrelia antigen patent, March 2001

Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. journal, July 1984

Osp A and B Sequence of Borrelia burgdonferi strains ACA1 and IP90 patent, July 1998

General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. journal, August 1985

Osp A proteins of Borrelia burgdorferi subgroups, encoding genes and vaccines patent, August 1999

Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit. journal, January 1986

Non-immunogenic polypeptides patent, December 1979

Replacing the complementarity-determining regions in a human antibody with those from a mouse journal, May 1986

Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults journal, December 1996

Expression of tetanus toxin fragment C in E.coli : high level expression by removing rare codons journal, January 1989

Immunometric assays using monoclonal antibodies patent, March 1983

Humanized immunoglobulins patent, December 1997

Structural identification of a key protective B-cell epitope in lyme disease antigen OspA journal, October 2000

Abilities of OspA proteins from different seroprotective groups of Borrelia burgdorferi to protect hamsters from infection. journal, January 1995

SV40 DNA transfection of cells in suspension: analysis of the efficiency of transcription and translation of T-antigen journal, March 1981

Inhibition of Borrelia burgdorferi-Tick Interactions In Vivo by Outer Surface Protein A Antibody journal, June 2001

A comprehensive set of sequence analysis programs for the VAX journal, January 1984

Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi sensu stricto and Borrelia afzelii strains but reveals major subgroups within the Borrelia garinii species journal, August 1995

Immunization with a polyvalent OspA vaccine protects mice against Ixodes ricinus tick bites infected by Borrelia burgdorferi ss, Borrelia garinii and Borrelia afzelii journal, October 1997

Amino acid substitution matrices from protein blocks. journal, November 1992

Chimeric proteins comprising borrelia polypeptides and uses therefor patent, June 2001

Osp a proteins of Borrelia burgdorferi subgroups, encoding genes and vaccines
patent, January 2004

Gene Synthesis[New Synthetic Methods(77)]
journal, June 1989

Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab
journal, April 1997

Reshaping human antibodies: grafting an antilysozyme activity
journal, March 1988

Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi
journal, April 1989

Recombinant constructs of Borrelia burgdorferi
patent, March 2006

Structure-based Design of a Second-generation Lyme Disease Vaccine Based on a C-terminal Fragment of Borrelia burgdorferi OspA
journal, July 2005

[14] Protein biotinylation
book, January 1990

Novel pharmaceutically active N-(2-aminoacylamido-2-deoxy-hexosyl)-amides, -carbamates and -ureas
patent, August 1989

Effects of amino acid sequence changes on antibody-antigen interactions
journal, January 1994

Borrelia antigen
patent, November 1997

Method of making a projection viewable transparency comprising an electrostatographic toner image
patent, August 1993

Use of deoxyinosine-containing primers vs degenerate primers for polymerase chain reaction based on ambiguous sequence information
journal, April 1994

Identification of LFA-1 as a Candidate Autoantigen in Treatment-Resistant Lyme Arthritis
journal, July 1998

Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes
journal, May 1986

Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor
journal, August 2000

Genetic Analysis of Protein Stability and Function
journal, December 1989

Analysis of the Lipidated Recombinant Outer Surface Protein A fromBorrelia burgdorferiby Mass Spectrometry
journal, March 1997

Enhanced Production of Recombinant Mycobacterium tuberculosis Antigens in Escherichia coli by Replacement of Low-Usage Codons
journal, January 2000

Using Codon Usage to Predict Genes Origin: Is the Escherichia coli Outer Membrane a Patchwork of Products from Different Genomes?
journal, January 1997

From genes to protein structure and function: novel applications of computational approaches in the genomic era
journal, January 2000

Antibodies that react with predetermined sites on proteins
journal, February 1983

Immunological adjuvant and process for preparing the same, pharmaceutical compositions, and process
patent, October 1989

Prodrugs of Peptides and Proteins for Improved Formulation and Delivery
journal, April 1993

Improved tools for biological sequence comparison.
journal, April 1988

Borrelia antigen
patent, July 2000

Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
journal, September 1979

Strategies for Delivery of Peptides Utilizing Absorption-Enhancing Agents
journal, December 1996

Recombinant immunoglobin preparations
patent, March 1989

Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA.
journal, January 1993

An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis.
journal, January 1993

Compositions and methods for administering Borrelia burgdorferi antigens
patent, August 2006

Enhanced evolutionary PCR using oligonucleotides with inosine at the 3′-terminus
journal, January 1991

A new technique for the assay of infectivity of human adenovirus 5 DNA
journal, April 1973

Safety and Immunogenicity of a Recombinant Outer Surface Protein A Lyme Vaccine
journal, June 1994

Purification of Borrelia burgdorferi outer surface protein A (OspA) and analysis of antibody binding domains.
journal, January 1994

Reactivity with a specific epitope of outer surface protein A predicts protection from infection with the Lyme disease spirochete, Borrelia burgdorferi.
journal, January 1997

Borrelia burdorferi Osp A and B proteins and immunogenic peptides
patent, November 2000

Altered ospa of borrelia burgdorferi
patent-application, December 2009

By-passing immunisation
journal, September 1992

Reshaping human antibodies for therapy
journal, March 1988

Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains.
journal, November 1984

Approaches toward the Directed Design of a Vaccine against Borrelia burgdorferi
journal, February 2002

A Vaccine Consisting of Recombinant Borrelia burgdorferi Outer-Surface Protein A to Prevent Lyme Disease
journal, July 1998

Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant
journal, July 1998

By-passing immunization: Human antibodies from V-gene libraries displayed on phage
journal, December 1991

Continuous cultures of fused cells secreting antibody of predefined specificity
journal, August 1975

Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
journal, July 1963

Preparation and use of polyethylene glycol propionaldehyde
patent, October 1993

Basic local alignment search tool
journal, October 1990

Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine.
journal, January 1996

A general method applicable to the search for similarities in the amino acid sequence of two proteins
journal, March 1970

OspA DNA and lyme disease vaccine
patent, February 2001

Comparison of biosequences
journal, December 1981

Induction of CD8⁺ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs
journal, April 1990

The Lyme disease vaccine candidate outer surface protein A (OspA) in a formulation compatible with human use protects mice against natural tick transmission of B. burgdorferi
journal, January 1995

Borrelia antigen
patent, March 2001

Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid.
journal, July 1984

Osp A and B Sequence of Borrelia burgdonferi strains ACA1 and IP90
patent, July 1998

General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids.
journal, August 1985

Osp A proteins of Borrelia burgdorferi subgroups, encoding genes and vaccines
patent, August 1999

Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit.
journal, January 1986

Non-immunogenic polypeptides
patent, December 1979

Replacing the complementarity-determining regions in a human antibody with those from a mouse
journal, May 1986

Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults
journal, December 1996

Expression of tetanus toxin fragment C in E.coli : high level expression by removing rare codons
journal, January 1989

Immunometric assays using monoclonal antibodies
patent, March 1983

Humanized immunoglobulins
patent, December 1997

Structural identification of a key protective B-cell epitope in lyme disease antigen OspA
journal, October 2000

Abilities of OspA proteins from different seroprotective groups of Borrelia burgdorferi to protect hamsters from infection.
journal, January 1995

SV40 DNA transfection of cells in suspension: analysis of the efficiency of transcription and translation of T-antigen
journal, March 1981

Inhibition of Borrelia burgdorferi-Tick Interactions In Vivo by Outer Surface Protein A Antibody
journal, June 2001

A comprehensive set of sequence analysis programs for the VAX
journal, January 1984

Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi sensu stricto and Borrelia afzelii strains but reveals major subgroups within the Borrelia garinii species
journal, August 1995

Immunization with a polyvalent OspA vaccine protects mice against Ixodes ricinus tick bites infected by Borrelia burgdorferi ss, Borrelia garinii and Borrelia afzelii
journal, October 1997

Amino acid substitution matrices from protein blocks.
journal, November 1992

Chimeric proteins comprising borrelia polypeptides and uses therefor
patent, June 2001

Applications and statistics for multiple high-scoring segments in molecular sequences.
journal, June 1993

Humanized immunoglobulins
patent, December 1996