Heterologous strain challenge of cattle immunized with Anaplasma marginale outer membranes

Palmer, Guy H.; Munodzana, Devere; Tebele, N; Ushe, T C; McElwain, Terry F.

doi:10.1016/0165-2427(94)90072-8

Cited by 20 publications

(8 citation statements)

References 17 publications

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“…Animals that control the infection remain persistently infected for life and serve as reservoirs for infection of naïve animals. Immunization with a fraction enriched for A. marginale outer membranes (OM) can induce complete protection against bacteremia and disease following experimental infection (13,44,52,61,70). Protective immunity correlates with CD4 ϩ T-cell responses and T-cell-dependent immunoglobulin G2 (IgG2) responses to OM antigens (13).…”

mentioning

confidence: 99%

Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine

Sutten

Norimine

Beare³

et al. 2010

Infect Immun

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Anaplasma and related Ehrlichia spp. are important tick-borne, Gram-negative bacterial pathogens of livestock and humans that cause acute infection and disease and can persist. Immunization of cattle with an Anaplasma marginale fraction enriched in outer membranes (OM) can provide complete protection against disease and persistent infection. Serological responses of OM vaccinees to the OM proteome previously identified over 20 antigenic proteins, including three type IV secretion system (T4SS) proteins, VirB9-1, VirB9-2, and VirB10. Subsequent studies showed that these three proteins also stimulated CD4؉ T-cell responses in OM vaccinees. The T4SS, composed of a complex of proteins spanning the inner and outer membranes of certain bacteria, is an important virulence factor but is relatively unexplored as a vaccine target. The goal of this study was to determine if additional T4SS proteins are immunogenic for animals immunized with the protective OM fraction of A. marginale. T4SS proteins expressed by in vitro transcription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins in Escherichia coli and their immunogenicity was verified. VirB2, a putative VirB7, VirB11, and VirD4 were immunogenic for OM vaccinees expressing several common major histocompatibility complex (MHC) class II haplotypes. VirB2 is encoded by multiple genes that share a conserved central region, and epitope mapping revealed T-cell epitopes in this region. The discovery of novel immunogenic T4SS proteins recognized by outbred individuals with common MHC haplotypes further justifies evaluating the T4SS as a potential vaccine candidate for pathogenic bacteria.

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confidence: 99%

Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine

Sutten

Norimine

Beare³

et al. 2010

Infect Immun

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“…Em bovinos, sabe-se que a imunização com membrana externa de A. marginale induz proteção contra desafio com isolado homólogo e heterólogo dessa riquétsia, a qual está correlacionada com os títulos de anticorpos contra as proteínas de membrana, incluindo a MSP5 , Palmer et al 1994b. No entanto, a imunização com MSP5 nativa não protegeu contra desafio com isolado homólogo de A. marginale .…”

Section: Msp5unclassified

Progressos na imunização contra Anaplasma marginale

et al. 2003

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Até o presente momento, as imunizações contra anaplasmose em rebanhos bovinos utilizam organismos vivos ou mortos. No entanto, esforços têm sido realizados nos últimos anos com o objetivo de desenvolver uma nova geração de vacinas. A membrana externa de Anaplasma marginale é capaz de induzir reposta imune protetora contra desafio homólogo e parcialmente protetora contra desafio heterólo-go. Nela foram identificadas seis proteínas principais de superfície (MSPs), as quais têm sido alvo de estudos para o desenvolvimento de imunógenos contra a anaplasmose. Destas proteínas, MSP1a e MSP2 têm demonstrado maior potencial como imunógenos, protegendo os animais contra desafio com isolados virulentos homólogos e heterólogos de A. marginale, apesar do polimorfismo de tamanho da primeira proteína e variabilidade do gene que codifica a segunda. Uma outra alternativa para a imunização contra A. marginale é o cultivo in vitro dessa riquétsia. Organismos inativados provenientes de cultivo em células IDE8 de Dermacentor variabilis foram testados como imunógeno. Os animais apresentaram uma significativa diferença na redução do volume globular após desafio e não apresentaram sinais clínicos de anaplasmose. Além da proteção conferida por este tipo de imunógeno, os organismos provenientes de cultura de células de carrapato são livres de células e patógenos de bovinos, o que é uma vantagem significativa quando comparado aos processos tradicionais de imunização.

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“…Immunity against acute A. marginale rickettsemia is directed against outer membrane surface proteins, and infectivity can be neutralized with antibodies against surface exposed epitopes (18,20,21). Correspondingly, cattle immunized with A. marginale outer membranes develop significantly lower rickettsemia following challenge than do adjuvant-immunized controls (20,22,27). Sera from these immunized and protected cattle recognize six major surface proteins (MSPs), and antibody titers against MSP2 and MSP5 correlate with protection against challenge with the homologous strain (20,22,27).…”

mentioning

confidence: 99%

“…Correspondingly, cattle immunized with A. marginale outer membranes develop significantly lower rickettsemia following challenge than do adjuvant-immunized controls (20,22,27). Sera from these immunized and protected cattle recognize six major surface proteins (MSPs), and antibody titers against MSP2 and MSP5 correlate with protection against challenge with the homologous strain (20,22,27). In contrast to protection induced by immunization with whole outer membranes or a native MSP1a/MSP1b complex, isolated recombinant-expressed MSPs, either alone or in combination, fail to induce comparable protection against rickettsemia (17,18,20,27).…”

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confidence: 99%

Conformational Dependence ofAnaplasma marginaleMajor Surface Protein 5 Surface-Exposed B-Cell Epitopes

et al. 1998

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The Anaplasma marginale outer membrane is composed of immunogenic major surface proteins (MSPs) linked both covalently and noncovalently in multimeric complexes (M. C. Vidotto, T. C. McGuire, T. F. McElwain, G. H. Palmer, and D. P. Knowles, Infect. Immun. 62:2940–2946). Consequently, effective induction of antibody against surface-exposed MSP epitopes has been postulated to require maintenance of MSP secondary through quatenary structures. Using MSP5 as a model and the approach of epitope mapping with recombinant expressed full-length and truncated proteins, we demonstrated that the immunodominant surface epitope bound by monoclonal antibody (MAb) ANAF16C1 required disparate amino- and carboxy-terminal regions of MSP5, indicating the conformational dependence of this epitope. The required amino-terminal MSP5 region included the cysteines involved in intramolecular disulfide bonding. The dependence of the immunodominant epitope on disulfide bonding was confirmed by loss of MAb ANAF16C1 binding to MSP5 following disulfide bond reduction and covalent modification of the reduced sulfhydryl groups. The recognition of the MSP5 immunodominant epitope by antibody induced by protective immunization with A. marginale outer membranes was also conformationally dependent, as shown by the loss of epitope binding following serum adsorption with native but not reduced and denaturedA. marginale. Importantly, the antibody response to all immunodominant MSP5 surface epitopes was restricted to conformationally dependent epitopes, since the binding of polyclonal anti-MSP5 antibody to the A. marginale surface could be blocked by adsorption with native but not denatured and reduced MSP5. These results confirm the importance of the secondary and tertiary structures of MSP epitopes as immune system targets and support the testing of immunogens which maintain the required conformation.

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Heterologous strain challenge of cattle immunized with Anaplasma marginale outer membranes

Cited by 20 publications

References 17 publications

Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine

Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine

Progressos na imunização contra Anaplasma marginale

Conformational Dependence ofAnaplasma marginaleMajor Surface Protein 5 Surface-Exposed B-Cell Epitopes

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