Inability of outer-surface protein C (OspC)-primed mice to elicit a protective anamnestic immune response to a tick-transmitted challenge of Borrelia burgdorferi

Gilmore, Robert D.; Bacon, Rendi Murphree; Carpio, Amber M.; Piesman, Joseph; Dolan, Marc C.; Mbow, Moustapha

doi:10.1099/jmm.0.05068-0

Cited by 22 publications

(18 citation statements)

References 29 publications

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“…Although vaccination of mice with OspC protein has been demonstrated to be protective, the protection is strain specific (6,16,17,32,37,46). This observation suggests that the protective epitopes likely reside within OspC type-specific domains.…”

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confidence: 84%

OspC Phylogenetic Analyses Support the Feasibility of a Broadly Protective Polyvalent Chimeric Lyme Disease Vaccine

Earnhart

Marconi

2007

Clin Vaccine Immunol

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confidence: 84%

OspC Phylogenetic Analyses Support the Feasibility of a Broadly Protective Polyvalent Chimeric Lyme Disease Vaccine

Earnhart

Marconi

2007

Clin Vaccine Immunol

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“…OspA was the immunogen of choice because it is a proven vaccine candidate against B. burgdorferi via the parenteral route (16,18) in addition to inducing a protective immune response when administered orally as purified antigen (34) or as recombinant Escherichia coli (17,21). Although there have been many studies to find additional vaccine candidates for Lyme disease (5,12,13,19,20,25,48), OspA is still the most effective immunogen against this pathogen. Following the discovery of a controversial autoantigenic epitope in OspA (24), we substituted this epitope in its sequence before cloning it into L. plantarum.…”

Section: Discussionmentioning

confidence: 99%

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Río

Dattwyler

Aroso

et al. 2008

Clin Vaccine Immunol

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Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.Lactic acid bacteria are naturally associated with mucosal surfaces, particularly the gastrointestinal tract, and are also indigenous to food-related habitats, including plants, wine, milk, and meat. These gram-positive bacteria include both important pathogens, e.g., several Streptococcus species, and extremely valuable nonpathogenic species that have been used since ancient times for food and feed fermentation (11,37,58). The host is highly adapted to the presence of commensal intestinal bacteria (36). There is evidence that some strains of lactic acid bacteria have a favorable influence on physiologic and pathological processes of the host due to their specific health-promoting probiotic characteristics that relate to modulation of the immune system (15,36,41). Some strains of lactic acid bacteria polarize the naïve immune system by skewing it toward Th1 responses (41, 56).There have been a number of reports of oral vaccine candidates established from genetically modified pathogenic bacteria, such as Salmonella and Listeria species (1, 2, 30, 45, 52), or commensal bacteria, such as Lactococcus lactis and Lactobacillus species (27,31,32,60). The latter are food-grade bacteria that have GRAS status (generally regarded as safe). While both pathogenic and commensal bacteria have advantages and disadvantages as mucosal delivery vehicles, lactic acid bacteria are preferable in terms of safety and a lower risk of side effects (27,47). Presentation of antigens on the surface of lactobacilli is attractive for vaccine design, especially because the peptidoglycan layer of some strains appears to exhibit natural immuno-adjuvanticity (33,35,44,46). Thus, these species are excellent candidates for the development of safe mucosal delivery vehicles of prophylactic and therapeutic molecules. Of the Lactobacillus strains previously used for vaccine delivery, we chose L. plantarum because there is evidence that this strain is a better agent for vaccination with tetanus toxin fragment C (TTFC) than L. casei or L. lactis (22,53).Lyme disease is the most prevalent vector-borne infectious disease in the United States. A vaccine administered via needle inoculation and based on outer surface protein A (OspA) has proved effective in preventing Borrelia burgdorferi infection in animals and humans (7,10,(16)(17)...

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“…Needle-inoculated pooled mouse sera (a gift from P. Rosa) was generated by the injection of RML white mice with 10 3 B. burgdorferi intradermally, with subsequent bleeds on 21 to 28 days postinfection (dpi) and was used at a 1:1,000 dilution. Tick bite sera were obtained from the white-footed mouse Peromyscus leucopus (the natural reservoir for Borrelia in the United States) at ϳ30 dpi or ICR mice (ϳ18 dpi) as previously reported (9,22) and used at a dilution of 1:1,000. Rabbit hyperimmune antiserum raised against live, low-passage B. burgdorferi B31 was produced as previously described and used at a dilution of 1:10,000 (9, 10).…”

Section: Methodsmentioning

confidence: 99%

Serologic Proteome Analysis ofBorrelia burgdorferiMembrane-Associated Proteins

2006

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Lyme disease, a global health concern, is caused by infection with Borrelia burgdorferi, B. afzelii, or B. garinii. The spirochete responsible for the disease in the United States is B. burgdorferi and is spread by the bite of an infected Ixodes tick. We utilized multiple two-dimensional gel techniques combined with proteomics to reveal the full humoral immune response of mice and Lyme patients to membrane-associated proteins isolated from Borrelia burgdorferi. Our studies indicated that a subset of immunogenic membrane-associated proteins (some new and some previously identified) was recognized by mice experimentally infected with Borrelia burgdorferi either by low-dose needle inoculation or by tick infestation. Moreover, the majority of these immunogenic membrane-associated proteins were recognized by sera from patients diagnosed with early-disseminated Lyme disease. These included RevA, ErpA, ErpP, DbpA, BmpA, FtsZ, ErpB, LA7, OppA I, OppA II, OppA IV, FlhF, BBA64, BBA66, and BB0323. Some immunogens (i.e., BBI36/38) were more reactive with sera from mice than Lyme patients, while additional membrane proteins (i.e., FlaB, P66, LA7, and Hsp90) were recognized more strongly with sera from patients diagnosed with early-localized, early-disseminated, or late (chronic)-stage Lyme disease. We were able to examine the humoral response in Lyme patients in a temporal fashion and to identify the majority of immunoreactive proteins as the disease progresses from early to late stages. This serologic proteome analysis enabled the identification of novel membrane-associated proteins that may serve as new diagnostic markers and, more importantly, as second-generation vaccine candidates for protection against Lyme disease.

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Inability of outer-surface protein C (OspC)-primed mice to elicit a protective anamnestic immune response to a tick-transmitted challenge of Borrelia burgdorferi

Cited by 22 publications

References 29 publications

OspC Phylogenetic Analyses Support the Feasibility of a Broadly Protective Polyvalent Chimeric Lyme Disease Vaccine

OspC Phylogenetic Analyses Support the Feasibility of a Broadly Protective Polyvalent Chimeric Lyme Disease Vaccine

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Serologic Proteome Analysis ofBorrelia burgdorferiMembrane-Associated Proteins

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