Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2

Johnson, Barbara J. B.; Sviat, Steven L.; Happ, Christine M.; Dunn, John J.; Frantz, J C; Mayer, Leonard W.; Piesman, Joseph

doi:10.1016/0264-410x(95)00035-y

Cited by 54 publications

(56 citation statements)

References 36 publications

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“…The lipid moiety of the 273-amino acid (aa) OspA, tripalmitoyl-S-glyceryl-cysteine (Pam3Cys), conveys adjuvant activity for antibody (Ab) production, most probably by amplifying Th cell responses through engagement of Toll-like 2-Toll-like 1/6 receptor heterodimers [4][5][6]. Unmodified OspA, in contrast, expresses only marginal immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

et al. 2005

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The immunogenicity of peptides and protein fragments can be considerably enhanced by their presentation on particulate carriers such as capsid‐like particles (CLP) from hepatitis B virus (HBV). Here we tested the suitability of the HBV capsid protein as a carrier for a relevant full‐length pathogen‐derived protein antigen. The entire 255‐amino acid ectodomain of the outer surface protein A (OspA) from Borrelia burgdorferi, the causative agent of Lyme disease, was inserted into the major B cell epitope of the HBV capsid, yielding a multimerization‐competent fusion protein, termed coreOspA. CoreOspA, consisting only in part of regular CLP, induced antibodies to OspA, including the Ig isotype profile and specificity for the protective epitope LA‐2, with an efficiency similar to that of recombinant lipidated OspA, the first generation vaccine against Lyme disease. Moreover, coreOspA actively and passively protected mice against subsequent challenge with B. burgdorferi. The data demonstrate the capacity of the HBV capsid protein to act as a potent immunomodulator even for full‐length and structurally complex polypeptide chains and thus opens new avenues for novel vaccine designs.

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Section: Introductionmentioning

confidence: 99%

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

et al. 2005

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“…However, all mice that were protected after challenge (80%) showed a high titer (OD 450 of Ͼ1) of total IgG specific to OspA: serum from all of these mice neutralized B. burgdorferi in culture, but only 75% of these had a large amount of LA-2 equivalent antibody in the serum. In Johnson et al (30), all 36% of hamsters that were protected after challenge had a high titer of total IgG specific to OspA, but only 60% of these had a large amount of LA-2 equivalent antibody. In another study (33) the natural reservoir host of B. burgdorferi senso lato, the yellow-necked mouse (Apodemus flavicollis), was immunized intraperitoneally with a suspension of lipidated OspA and subsequently tick challenged.…”

Section: Discussionmentioning

confidence: 92%

“…Thus, our correlate of protection was set at a conservative OD 450 of Ͼ1 equivalent titer of OspA-specific IgG. Differences in vaccine efficacy are due to the fact that the bait vaccine used in this study expresses the lipidated form of OspA as well as in the study by Kurtenback et al (33), while in the hamster (30), the unlipidated form of OspA was used.…”

Section: Discussionmentioning

confidence: 99%

“…burgdorferi IgG antibodies in serum from vaccinated mice after challenge. A pattern of 5 out of 10 bands positive (93,66,58,45,41,39,30,28,23, and 18 kDa) was considered evidence of infection.…”

Section: Methodsmentioning

confidence: 99%

“…Through our extensive experimentation with the OspA-RTV formulation and P. leucopus over the past 6 years, we observed that an effective immune response could be measured by a titer of antibody specific to OspA equivalent to an OD 450 of Ն1. The LA-2 equivalent antibody assay is generally accepted as a good correlate of vaccine protection (30). To test our hypothesis, we analyzed the LA-2 equivalent antibody present in the serum from whitefooted mice after consumption of the bait RTV and evaluated its correlation to protection as measured by a neutralization assay and by assessment of B. burgdorferi dissemination in the mouse after challenge by PCR.…”

Section: Host Reservoir Competence and Vector Transmission Probabilitymentioning

confidence: 99%

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Reservoir Targeted Vaccine for Lyme Borreliosis Induces a Yearlong, Neutralizing Antibody Response to OspA in White-Footed Mice

Richer

Aroso

Contente-Cuomo

et al. 2011

Clin Vaccine Immunol

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Lyme disease is caused by the spirochete Borrelia burgdorferi. The enzootic cycle of this pathogen requires that Ixodes spp. acquire B. burgdorferi from infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to control B. burgdorferi; there is no human vaccine available, and existing vector control measures are generally not acceptable to the public. However, if B. burgdorferi could be eliminated from its reservoir hosts or from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. We developed OspA-RTV, a reservoir targeted bait vaccine (RTV) based on the immunogenic outer surface protein A (OspA) of B. burgdorferi aimed at breaking the natural cycle of this spirochete. White-footed mice, the major reservoir species for this spirochete in nature developed a systemic OspA-specific IgG response as a result of ingestion of the bait formulation. This immune response protected white-footed mice against B. burgdorferi infection upon tick challenge and cleared B. burgdorferi from the tick vector. In performing extensive studies to optimize the OspA-RTV for field deployment, we determined that mice that consumed the vaccine over periods of 1 or 4 months developed a yearlong, neutralizing anti-OspA systemic IgG response. Furthermore, we defined the minimum number of OspA-RTV units needed to induce a protective immune response.Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in North America and Europe (2), and the area of where the disease is endemic is expanding (28,39,57). B. burgdorferi infection produces a progressive disease with a wide array of clinical manifestations involving the skin, heart, joints, and central and peripheral nervous system (46,(49)(50)(51). Disseminated infection can cause permanent damage to some of these systems (50). Lyme disease can be successfully treated with antibiotics, but recovery can involve a substantial convalescence period (31,40,41,58). No human vaccine is commercially available.In eastern North America, B. burgdorferi is transmitted among wildlife hosts and humans by Ixodes scapularis (1,4,5,34). I. scapularis has a 2-year life cycle with four life-stages: egg, larva, nymph and adult (1). The nymph is the tick life stage that infects humans (3,26,55). Control measures aimed at disrupting the triad vector-B. burgdorferi-vertebrate reservoir (54) will reduce the prevalence of B. burgdorferi and consequently should reduce the incidence of human Lyme disease.Oral immunization is not invasive, and it is suitable for economical mass vaccination campaigns. Outer surface protein A (OspA) remains the most effective vaccine candidate against B. burgdorferi, with an efficacy of 80 to 100% in mice (20)(21)(22)(23)25) and 75 to 80% in humans (52). We have shown that an OspA-based vaccine delivered via oral gavage inoculation or delivered as bait breaks the transmission cycle of B. burgdorferi in the Lyme disease mouse model the Mus...

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Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter

et al. 1996

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Plasmid DNA encoding the outer surface lipoprotein A (OspA) of Borrelia burgdorferi under the control of either strong eukaryotic/viral or its own bacterial promoter was injected intramuscularly (m. tibialis anterior) or intradermally into BALB/c and AKR/N mice. OspA-specific antibodies and OspA-reactive T helper 1 cells (Th1) were induced only with those plasmids containing the ospA structural gene including its own regulatory control region immediately upstream. In the absence of the ospA promoter, no or only marginal immune responses to OspA were obtained, even when strong eukaryotic promoter/enhancer elements were present. Together with the finding that the ospA promoter is active in a mouse B-lymphoma line, the data suggest that spirochetes are able to express at least part of their genes in the mammalian environment. Mice previously vaccinated with the relevant ospA plasmid DNA were protected against subsequent experimental challenge with a virulent strain of B. burgdorferi, as measured by the appearance of antibodies to a prominent protective epitope (LA-2) and the failure to re-isolate spirochetes from ear biopsies. In addition, C.B-17 severe-combined immunodeficient mice could be protected against infection by passive transfer of immune sera from ospA plasmid DNA-inoculated normal mice. Protective LA-2-related antibody titers obtained after repeated immunization persisted for 200 days and longer. This simple procedure of immunization using plasmid DNA consisting of a prokaryotic gene under the control of its own promoter holds great promise for the development of alternative subunit vaccines against bacterial infections, including Lyme disease. In addition, the availability of this novel prokaryotic promoter element now allows the study of the basis for the differential expression of bacterial genes in prokaryotic and eukaryotic environments.

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Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2

Cited by 54 publications

References 36 publications

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

Reservoir Targeted Vaccine for Lyme Borreliosis Induces a Yearlong, Neutralizing Antibody Response to OspA in White-Footed Mice

Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter

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