Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2

Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high...

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Published inVaccine Vol. 13; no. 12; pp. 1086 - 1094
Main Authors Johnson, Barbara J.B., Sviat, Steven L., Happ, Christine M., Dunn, John J., Frantz, Joseph C., Mayer, Leonard W., Piesman, Joseph
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 01.08.1995
Elsevier
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Abstract Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals—59–79%, depending on the challenge strain and route—against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks ( Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml −1 of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.
AbstractList Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals--59-79%, depending on the challenge strain and route--against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks (Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml-1 of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.
Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals—59–79%, depending on the challenge strain and route—against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks ( Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml −1 of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.
Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals-59-79%, depending on the challenge strain and route-against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks (Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml super(-1) of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.
Author Mayer, Leonard W.
Piesman, Joseph
Johnson, Barbara J.B.
Sviat, Steven L.
Happ, Christine M.
Dunn, John J.
Frantz, Joseph C.
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  organization: Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
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Issue 12
Keywords outer surface protein
Lyme disease
Borrelia burgdorferi
vaccine
LA-2 antibody
Immune response
Spirochaetaceae
Spirochaetales
Antigenic determinant
Rodentia
Borrelia infection
Vaccine
Cell surface
Infection
Vertebrata
Mammalia
Immunogenicity
Bacteriosis
Bacteria
Hamster
Humoral immunity
Spirachaetosis
Language English
License CC BY 4.0
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Snippet Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We...
Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We...
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SubjectTerms Animals
Antibodies, Bacterial - blood
Antibodies, Monoclonal - immunology
Antigens, Surface - immunology
Bacterial Outer Membrane Proteins - immunology
Bacterial Vaccines - immunology
Bacteriology
Biological and medical sciences
Borrelia burgdorferi
Borrelia burgdorferi Group - immunology
Cricetinae
Epitopes
Female
Fundamental and applied biological sciences. Psychology
hamster
LA-2 antibody
Lipoproteins
Lyme disease
Lyme Disease - prevention & control
Mesocricetus
Microbiology
outer surface protein
Vaccination
vaccine
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, Synthetic - immunology
Title Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2
URI https://dx.doi.org/10.1016/0264-410X(95)00035-Y
https://www.ncbi.nlm.nih.gov/pubmed/7491816
https://search.proquest.com/docview/16873092
https://search.proquest.com/docview/77724438
Volume 13
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