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Infection and Immunity, November 1998, p. 5379-5387, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
DbpA, but Not OspA, Is Expressed by Borrelia
burgdorferi during Spirochetemia and Is a Target for
Protective Antibodies
David R.
Cassatt,*
Nita K.
Patel,
Nancy D.
Ulbrandt, and
Mark S.
Hanson
MedImmune, Inc., Gaithersburg, Maryland 20878
Received 29 June 1998/Returned for modification 11 August
1998/Accepted 28 August 1998
DbpA is a target for antibodies that protect mice against infection
by cultured Borrelia burgdorferi. Infected mice exhibit early and sustained humoral responses to DbpA and DbpB, suggesting that
these proteins are expressed in vivo. Many antigens expressed in
mammals by B. burgdorferi are repressed in vitro at lower
growth temperatures, and we have now extended these observations to
include DbpA and DbpB. To confirm that the protective antigen DbpA is expressed in vivo and to address the question of its accessibility to
antibodies during infection, we examined B. burgdorferi in blood samples from mice following cutaneous inoculation. B. burgdorferi was visualized by dark-field microscopy in plasma
samples from spirochetemic mice, and an indirect immunofluorescence
assay showed that these spirochetes were DbpA positive and OspA
negative. We developed an ex vivo borreliacidal assay to show that
hyperimmune antiserum against DbpA, but not OspA, killed these
plasma-derived spirochetes, demonstrating that DbpA is accessible to
antibodies during this phase of infection. Blood transferred from
spirochetemic donor mice readily established B. burgdorferi
infection in naive recipient mice or mice hyperimmunized with OspA,
while mice hyperimmunized with DbpA showed significant protection
against challenge with host-adapted spirochetes. Antiserum from
persistently infected mice had borreliacidal activity against both
cultured and plasma-derived spirochetes, and adsorption of this serum
with DbpA substantially depleted this killing activity. Our
observations show that immunization with DbpA blocks B. burgdorferi dissemination from the site of cutaneous inoculation
and suggest that DbpA antibodies may contribute to control of
persistent infection.
*
Corresponding author. Mailing address: MedImmune, Inc.,
35 West Watkins Mill Rd., Gaithersburg, MD 20878. Phone: (301)
527-4308. Fax: (301) 527-4200. E-mail:
cassattd{at}medimmune.com.
Infection and Immunity, November 1998, p. 5379-5387, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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