Safety and Immunogenicity of an Outer Surface Protein A Vaccine in Subjects with Previous Lyme Disease

Schoen, Robert T.; Meurice, François; Brunet, Cristina; Cretella, Stella B.; Krause, David S.; Craft, Joe; Fikrig, Erol

doi:10.1093/infdis/172.5.1324

Cited by 59 publications

(27 citation statements)

References 14 publications

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“…burgdorferi antibodies, in particular anti-OspA antibodies, may be protective in Lyme disease; however, even healthy patients vaccinated with an OspA-containing formulation developed transient arthralgia (34). However, a reactive arthritis was not a universal finding in the OspA vaccine recipients (42).…”

Section: Discussionmentioning

confidence: 99%

Evidence ofBorreliaAutoimmunity-Induced Component of Lyme Carditis and Arthritis

et al. 2005

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We investigated the possibility that manifestations of Lyme disease in certain hosts, such as arthritis and carditis, may be autoimmunity mediated due to molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first compared amino acid sequences of Streptococcus pyogenes M protein, a known inducer of antibodies that are cross-reactive with myosin, and B. burgdorferi and found significant homologies with OspA protein. We found that S. pyogenes M5-specific antibodies and sera from B. burgdorferi-infected mice reacted with both myosin and B. burgdorferi proteins by Western blots and enzyme-linked immunosorbent assay. To investigate the relationship between self-reactivity and the response to B. burgdorferi, NZB mice, models of autoimmunity, were infected. NZB mice infected with B. burgdorferi developed higher degrees of joint swelling and higher anti-B. burgdorferi immunoglobulin M cross-reactive responses than other strains with identical major histocompatibility complex (DBA/2 and BALB/c). These studies reveal immunological crossreactivity and suggest that B. burgdorferi may share common epitopes which mimic self-proteins. These implications could be important for certain autoimmunity-susceptible individuals or animals who become infected with B. burgdorferi.

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Section: Discussionmentioning

confidence: 99%

Evidence ofBorreliaAutoimmunity-Induced Component of Lyme Carditis and Arthritis

et al. 2005

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“…species (Barbour et al 1984). A recombinant vaccine has been developed on the basis of this antigen (Schoen et al 1995). Considering the low level in horizontal plasmid transmission (Dykhuizen et al 1993), we used the OspA gene sequence to investigate the phylogenetic relationship between our samples and the sequences available in GenBank to infer population structure.…”

Section: Introductionmentioning

confidence: 99%

Borrelia lusitaniae OspA Gene Heterogeneity in Mediterranean Basin Area

Grego

Bertolotti

Peletto³

et al. 2007

J Mol Evol

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In this study, Borrelia lusitaniae DNA extracted from ticks and lizards was used to amplify the outer surface protein A (OspA) gene in order to increase knowledge about sequence variability in the Mediterranean basin area, to better understand how Borrelia lusitaniae has evolved and how its distribution has expanded. Phylogenetic trees including Italian and reference sequences showed a clear separation of B. lusitaniae OspA strains in two different major clades. North African isolates form a clade with Portuguese POTIB strains, whereas Italian samples are grouped with German strains and a human Portuguese strain. This subdivision was supported by very high posterior probability values in the trees, by both analysis of molecular variance and selective pressure. These results, based on phylogenetic information contained in the OspA gene sequences, show the presence of two different B. lusitaniae strains circulating in the Mediterranean basin area, suggesting two different evolution paths.

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“…It has been suggested that prior infection with B. burgdorferi sensu lato might blunt the immune response, resulting in a lower ability of seropositive subjects to mount an immune response to vaccination with OspA (26,27). Alternatively, because of the lipidated nature of the OspA vaccine and the high expression of lipoproteins by B. burgdorferi sensu lato, it is possible that the anti-lipoprotein antibodies induced in seropositive subjects by previous infection interfere with the induction of antibody responses against the OspA vaccine, such that higher antigen doses are required in the seropositive population.…”

Section: Discussionmentioning

confidence: 99%

“…One previous study of a monovalent OspA-1 vaccine investigated the antibody responses to vaccination in seropositive subjects, but this study did not include a head-to-head seronegative cohort (27). Because of the lack of a direct comparator group in this previous study and the use of a different assay format than those in studies on the same vaccine in seronegative populations (28)(29)(30)(31)(32)(33), it is not clear whether the previous monovalent OspA-1 vaccine induced similar antibody titers in seronegative and seropositive populations.…”

Section: Discussionmentioning

confidence: 99%

A Novel Multivalent OspA Vaccine against Lyme Borreliosis Is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi Sensu Lato

Wressnigg

Barrett

Pöllabauer

et al. 2014

Clin. Vaccine Immunol.

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Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 g or 60 g alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.)

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Safety and Immunogenicity of an Outer Surface Protein A Vaccine in Subjects with Previous Lyme Disease

Cited by 59 publications

References 14 publications

Evidence ofBorreliaAutoimmunity-Induced Component of Lyme Carditis and Arthritis

Evidence ofBorreliaAutoimmunity-Induced Component of Lyme Carditis and Arthritis

Borrelia lusitaniae OspA Gene Heterogeneity in Mediterranean Basin Area

A Novel Multivalent OspA Vaccine against Lyme Borreliosis Is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi Sensu Lato

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