Vaccination against Lyme Disease with Recombinant<i>Borrelia burgdorferi</i>Outer-Surface Lipoprotein A with Adjuvant

Steere, Allen C.; Sikand, Vijay K.; Meurice, François; Parenti, Dennis; Fikrig, Erol; Schoen, Robert T.; Nowakowski, John; Schmid, Christopher H.; Laukamp, Sabine; Buscarino, Charles; Krause, David S.

doi:10.1056/nejm199807233390401

Cited by 652 publications

(475 citation statements)

References 27 publications

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“…The fact that OspA-specific Ab, which block transmission of spirochetes by targeting and killing B. burgdorferi in the midgut of feeding ticks [10], are generated exclusively under artificial conditions emphasizes the notion that "efficient vaccines may need additional antigenic stimuli not available during natural infection" [1]. On the basis of such studies, a monovalent vaccine, consisting of the OspA lipoprotein, was developed [16] and shown to be efficacious in humans [19].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2003

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“…For example, altered HLA-peptide interaction has been proposed to explain the association of HLA-DRB1*0401 with chronic rheumatological sequelae (but not susceptibility to infection) caused by another spirochete, B. burgdorferi. 42 Assuming that individual HLA-DQ6 alleles were not associated with seropositivity, we hypothesized that the valine (Val 57 )/aspartic acid (Asp 57 ) polymorphism at position 57 of the HLA-DQ b chain, known to influence HLA-peptide binding, 43 could influence susceptibility to leptospirosis among DQ6 positive persons. The HLA-DQ6 position-57 residue was unambiguous for all 36 HLA-DQ6 positive triathletes.…”

Section: Resultsmentioning

confidence: 99%

HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis

et al. 2004

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“…Escherichia coli as the immunogen (Steere et al, 1998). The monovalent antigen is absorbed to aluminum hydroxide in phosphate buffered saline.…”

Section: E Vaccinementioning

confidence: 99%

“…LYMErix is given in three 30-µg doses at 0, one, and 12 months. The overall efficacy of the vaccine in an extensive phase II human trial (n=10,936) was 76% after three vaccine injections (Steere et al, 1998). The main adverse reaction reported was tenderness at the injection site and less than 1% of patients complained of headache, fatigue, or skin rash.…”

Section: E Vaccinementioning

confidence: 99%

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Characterization of secA-sod operon in Borrellia burgdorferi.

Nichols¹

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Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ 70 -like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed to be relatively lower amounts than sod. Both genes were expressed in all phases of growth, with greatest expression observed in stationary phase. Because transcription of most sod genes is tightly regulated by iron concentration, the secA-sod gene expression was analyzed in borrelial cells grown in varying amounts of metal. Ironrestriction did not significantly affect growth nor did it affect transcription of secA or sod.Likewise, no major differences in transcription were observed with restricting or supplementing media with manganese. To test the possibility that the borrelial SOD may function with either iron or manganese as a cofactor as in cambialistic SODs, SOD activity was assayed and the highest activity was observed in increased manganese concentrations.Protein expression profiles of Sh-2-82 cultured in metal-defined media were investigated by one-and two-dimensional gel electrophoresis. Approximately 15 proteins were differentially expressed in response to metal concentration. iv ACKNOWLEDGMENTS

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Vaccination against Lyme Disease with RecombinantBorrelia burgdorferiOuter-Surface Lipoprotein A with Adjuvant

Abstract: Three injections of vaccine prevented most definite cases of Lyme disease or asymptomatic B. burgdorferi infection.

Cited by 652 publications

References 27 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

HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis

Characterization of secA-sod operon in Borrellia burgdorferi.

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