Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen

Schaible, U. E.; Gern, Lise; Wallich, R; Kramer, Daniel; Prester, Marlot; Simon, Markus M.

doi:10.1016/0165-2478(93)90056-8

Cited by 58 publications

(69 citation statements)

References 15 publications

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“…Thus, spirochetes have evolved strategies to escape natural immunity and to persist in their mammalian hosts. However, the previous finding that a fraction of experimentally challenged AKR/N mice with high levels of OspC-specific Ab was able to resolve infection [20] and that IS from tick-or needle-infected mice prevent subsequent infection in naive recipients [4,5] suggested that inherent spirochetal defense mechanisms can be breached by more-potent and/or morewell-timed Ab responses. This has been most convincingly documented for Ab to OspA and OspC [10,16,20].…”

Section: Discussionmentioning

confidence: 99%

“…Besides Ab to OspA and OspB [16], which are only observed in § 10 8 but not in § tick and § 10 3 IS ( Fig. 1A; and [4]), all three IS contain Ab with protective potential that are specific for other known spirochetal structures, including OspC and DbpA, though at different levels (Fig. 1A).…”

Section: Immune Serum Raised Following Artificial Infection With Highmentioning

confidence: 95%

“…§ tick" IS) or infected experimentally with either low ( § 10 3 ) or high doses ( § 10 8 ) of B. burgdorferi (ZS7) contain Ab that are able to protect, upon passive transfer, naive recipients against subsequent challenge [4,5]. Besides Ab to OspA and OspB [16], which are only observed in § 10 8 but not in § tick and § 10 3 IS ( Fig.…”

Section: Immune Serum Raised Following Artificial Infection With Highmentioning

confidence: 99%

“…Previous studies in mice and man have shown that natural infection is accompanied by the generation of specific Ab with a time-dependent increase of their diversity [2,3]. However, in mice these pathogen-induced Ab are inefficient in resolving an established disease/infection but are able to prevent infection in naive recipients, upon passive transfer of Ab [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Artificial‐infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

et al. 2003

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Vaccination with recombinant outer surface protein A (OspA) from Borrelia burgdorferi provides excellent antibody-mediated protection against challenge with the pathogen in animal models and in humans. However, the bactericidal antibodies are ineffective in the reservoir host, since OspA is expressed by spirochetes only in the vector, but rarely, if at all, in mammals. Using an artificially generated immune serum (anti-10 8 spirochetes) with high protective potential for prophylactic and therapeutic treatment, we have now isolated from an expression library of B. burgdorferi (strain ZS7) three novel genes, zs7.a36, zs7.a66 and zs7.a68. All three genes are located, together with ospA/B, on the linear plasmid lp54, and are expressed in vitro and in ticks. At least temporarily two of them, ZS7.A36 and ZS7.A66, are also expressed during infection. The respective natural antigens are poorly immunogenic in infected normal mice but elicited antibodies in Lyme disease patients. We show that recombinant preparations of ZS7.A36, ZS7.A66 and ZS7.A68 induce functional antibodies in rabbits capable of protecting immunodeficient mice against subsequent experimental infection. These findings suggest that all three recombinant antigens represent potential candidates for a 'second generation' vaccine to prevent and/or cure Lyme disease.

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Section: Discussionmentioning

confidence: 99%

Section: Immune Serum Raised Following Artificial Infection With Highmentioning

confidence: 95%

Section: Immune Serum Raised Following Artificial Infection With Highmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Artificial‐infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

et al. 2003

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“…burgdorferi is the causative agent of Lyme disease, an increasingly common ailment of humans and several other mammals (15,48). Infection of a mammal by B. burgdorferi is generally accompanied by the production of antibodies directed against a limited number of bacterial antigens (17,19,41,52), several of which have been identified as surface-exposed lipoproteins. At least three of these lipoproteins, OspC, OspE, and OspF, are differentially expressed by B. burgdorferi, being produced in greater quantities by cultured bacteria that are shifted from 23 to 32ЊC than by those maintained at the lower temperature (43,49).…”

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confidence: 99%

A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

1996

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We have identified four loci in Borrelia burgdorferi B31 that contain open reading frames capable of encoding six proteins that are related to the antigenic proteins OspE and OspF. We have designated these proteins Erp, for OspEF-related protein, and named their respective genes erp. The erpA and erpB genes are linked, as are erpC and erpD, and the pairs probably constitute two operons. The erpG and erpH genes appear to be monocistronic. The ErpA and ErpC proteins are expressed by B. burgdorferi B31 in culture and are recognized by a polyclonal antiserum raised against the OspE protein of B. burgdorferi N40. The four erp loci are each located on different 32-kb circular plasmids that contain additional DNA sequences that are homologous to each other and to an 8.3-kb circular plasmid of B. burgdorferi sensu lato Ip21. All four 32-kb plasmids can be maintained within a single bacterium, which may provide a model for the study of plasmid replication and segregation in B. burgdorferi.Borrelia burgdorferi is a member of the order Spirochaetales, the spirochetes, an order that is phylogenetically and morphologically distinct from such well-characterized bacteria as Escherichia coli and Bacillus subtilis (8,24,34,35,53). B. burgdorferi bacteria naturally contain a wide variety of plasmids (4,13,25,40,42,45,47,54), yet nothing is known about the mechanisms by which plasmids are maintained in these bacteria. Several observations suggest that the small DNA species of B. burgdorferi and other spirochetes may be fundamentally different from the plasmids of other bacteria, the most significant being that there are linear plasmids in B. burgdorferi (4,5,7,13,22,23,42). Also, two B. burgdorferi genes involved in purine biosynthesis are located on a circular plasmid (29), which appears to be inconsistent with the classical definition of a plasmid as a nonessential extrachromosomal element. Other plasmids of B. burgdorferi appear to be capable of undergoing recombination to form multimeric plasmids (25, 31), and there have been reports of DNA sequences located on several different plasmids within the same bacterium (46,47,(54)(55)(56).B. burgdorferi is the causative agent of Lyme disease, an increasingly common ailment of humans and several other mammals (15,48). Infection of a mammal by B. burgdorferi is generally accompanied by the production of antibodies directed against a limited number of bacterial antigens (17,19,41,52), several of which have been identified as surface-exposed lipoproteins. At least three of these lipoproteins, OspC, OspE, and OspF, are differentially expressed by B. burgdorferi, being produced in greater quantities by cultured bacteria that are shifted from 23 to 32ЊC than by those maintained at the lower temperature (43, 49). For OspC, at least, this appears to be related to induction of specific protein synthesis by the spirochete in ticks following feeding upon a warm-blooded animal (43). Temperature-dependent differential expression of bacterial proteins that are involved in host infection has been o...

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Resolution of experimental and tick-borneBorrelia burgdorferiinfection in mice by passive, but not active immunization using recombinant OspC

et al. 1999

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Vaccination with outer surface protein A (OspA) of Borrelia burgdorferi prevents subsequent infection and disease in both laboratory animals and humans with high efficacy. OspA-based immunity, however, does not affect established infection due to the loss of OspA expression in the vertebrate host. We show here that repeated passive transfer of mouse and/or rabbit immune sera to recombinant GST-OspC fusion protein resulted in a dose-dependent resolution (1) of fully established arthritis and carditis as well as infection in needle-challenged C.B-17 SCID and (2) of infection in both experimentally and tick-infected BALB/c mice. Unexpectedly, active immunization of disease-susceptible AKR/N mice with GST-OspC only led to prevention but not resolution of disease and infection, in spite of high serum titers of OspC-specific Ab and the expression of ospC in tissue-derived spirochetes. The data suggest that the efficacy of OspC antibody-mediated immunity depends on the immunological history of the recipient and/or environment-dependent regulation of OspC surface expression by spirochetes in vivo. The results encourage further attempts to develop therapeutic vaccination protocols against Lyme disease.

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Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen

Cited by 58 publications

References 15 publications

Artificial‐infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

Artificial‐infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

Resolution of experimental and tick-borneBorrelia burgdorferiinfection in mice by passive, but not active immunization using recombinant OspC

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