Inability of Truncated Recombinant Osp A Proteins to Elicit Protective Immunity to Borrelia burgdorferi in Mice

Linda K. Bockenstedt, Erol Fikrig, Stephen W Barthold, Fred S. Kantor, Richard A. Flavell

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The murine immune response to Borrelia burgdorferi (Bb), the etiologic agent of Lyme disease, is characterized by the development of antibodies reactive with the outer surface protein (Osp) A. It has been demonstrated that passive immunization of mice with at least some Osp A antibodies, including an Osp A mAb (CIII.78) that binds to a conformational epitope in the carboxyl-terminus of Osp A, provides protection against Bb challenge. Active immunization of mice with Osp A also confers protection, making Osp A a candidate for a vaccine Ag. To determine the regions of the Osp A protein that can elicit protective immunity, we immunized and boosted mice with overlapping recombinant truncated fragments of Osp A, then challenged them with Bb. All groups of mice developed IgG Osp A antibodies detectable by immunoblotting with sera diluted at least 5000-fold. As expected, vaccination with full-length recombinant Osp A protected mice from challenge infection. In contrast, none of the mice vaccinated with the truncated Osp A proteins demonstrated immunity, even those immunized with an Osp A fragment binding the neutralizing mAb CIII.78. Osp A antibodies contained in the truncated Osp A antisera also failed to immunoprecipitate in vitro translated full-length Osp A and did not bind, as demonstrated by indirect immunofluorescence, to live or acetone-fixed Bb. Taken together, these results suggest that neutralizing Osp A antibodies are induced by vaccination with the full-length recombinant Osp A protein but not by vaccination with recombinant fragments.

Original languageEnglish (US)
Pages (from-to)900-906
Number of pages7
JournalJournal of Immunology
Volume151
Issue number2
StatePublished - Jul 15 1993
Externally publishedYes

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Borrelia burgdorferi
Immunity
Proteins
Vaccination
Antibodies
OspA protein
Borrelia burgdorferi Group
Passive Immunization
Lyme Disease
Indirect Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Immunology

Cite this

Inability of Truncated Recombinant Osp A Proteins to Elicit Protective Immunity to Borrelia burgdorferi in Mice. / Bockenstedt, Linda K.; Fikrig, Erol; Barthold, Stephen W; Kantor, Fred S.; Flavell, Richard A.

In: Journal of Immunology, Vol. 151, No. 2, 15.07.1993, p. 900-906.

Research output: Contribution to journalArticle

Bockenstedt, Linda K. ; Fikrig, Erol ; Barthold, Stephen W ; Kantor, Fred S. ; Flavell, Richard A. / Inability of Truncated Recombinant Osp A Proteins to Elicit Protective Immunity to Borrelia burgdorferi in Mice. In: Journal of Immunology. 1993 ; Vol. 151, No. 2. pp. 900-906.
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abstract = "The murine immune response to Borrelia burgdorferi (Bb), the etiologic agent of Lyme disease, is characterized by the development of antibodies reactive with the outer surface protein (Osp) A. It has been demonstrated that passive immunization of mice with at least some Osp A antibodies, including an Osp A mAb (CIII.78) that binds to a conformational epitope in the carboxyl-terminus of Osp A, provides protection against Bb challenge. Active immunization of mice with Osp A also confers protection, making Osp A a candidate for a vaccine Ag. To determine the regions of the Osp A protein that can elicit protective immunity, we immunized and boosted mice with overlapping recombinant truncated fragments of Osp A, then challenged them with Bb. All groups of mice developed IgG Osp A antibodies detectable by immunoblotting with sera diluted at least 5000-fold. As expected, vaccination with full-length recombinant Osp A protected mice from challenge infection. In contrast, none of the mice vaccinated with the truncated Osp A proteins demonstrated immunity, even those immunized with an Osp A fragment binding the neutralizing mAb CIII.78. Osp A antibodies contained in the truncated Osp A antisera also failed to immunoprecipitate in vitro translated full-length Osp A and did not bind, as demonstrated by indirect immunofluorescence, to live or acetone-fixed Bb. Taken together, these results suggest that neutralizing Osp A antibodies are induced by vaccination with the full-length recombinant Osp A protein but not by vaccination with recombinant fragments.",
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