T cell responses to bluetongue virus are directed against multiple and identical CD4+ and CD8+ T cell epitopes from the VP7 core protein in mouse and sheep

Rojas, José M.; Rodríguez-Calvo, Teresa; Peña, Lourdes; Sevilla, Noemı́

doi:10.1016/j.vaccine.2011.07.061

Cited by 36 publications

(46 citation statements)

References 32 publications

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“…These results confirm the role of the BTV VP7 protein in priming both CD4 + and CD8 + T-cell responses [16]. In agreement with a previous study [18], the vectors elicited detectable levels of VP7-binding but not neutralizing antibodies after immunization of sheep.…”

Section: Discussionsupporting

confidence: 92%

“…Immunization of sheep with inactivated vaccine is not consistently associated with T-cell immunity, depending on adjuvant and/or booster dose [22], [35]. Both CD4 + and CD8 + T-cell epitopes, recognized by T-cells from infected sheep, have been identified within the VP7 antigen [16]. VP7 is a major BTV group antigen and sheep vaccinated with VP7 encoded by a capripox vector were partially protected against heterologous challenge [18].…”

Section: Discussionmentioning

confidence: 99%

“…However, in addition to the B cell response, cytotoxic T lymphocytes (CTL) play a role in protection against BTV [14]. Among BTV proteins, VP7, NS1 and VP2 contain major T-cell epitopes [15], [16] but only the VP7 protein contains CD8 + T-cell epitopes that are conserved amongst BTV serotypes [17]. A recombinant capripoxvirus expressing VP7 of BTV-1 has proved to confer partial protection against a heterologous BTV-3 challenge [18].…”

Section: Introductionmentioning

confidence: 99%

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Expression of VP7, a Bluetongue Virus Group Specific Antigen by Viral Vectors: Analysis of the Induced Immune Responses and Evaluation of Protective Potential in Sheep

et al. 2014

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Bluetongue virus (BTV) is an economically important Orbivirus transmitted by biting midges to domestic and wild ruminants. The need for new vaccines has been highlighted by the occurrence of repeated outbreaks caused by different BTV serotypes since 1998. The major group-reactive antigen of BTV, VP7, is conserved in the 26 serotypes described so far, and its role in the induction of protective immunity has been proposed. Viral-based vectors as antigen delivery systems display considerable promise as veterinary vaccine candidates. In this paper we have evaluated the capacity of the BTV-2 serotype VP7 core protein expressed by either a non-replicative canine adenovirus type 2 (Cav-VP7 R0) or a leporipoxvirus (SG33-VP7), to induce immune responses in sheep. Humoral responses were elicited against VP7 in almost all animals that received the recombinant vectors. Both Cav-VP7 R0 and SG33-VP7 stimulated an antigen-specific CD4+ response and Cav-VP7 R0 stimulated substantial proliferation of antigen-specific CD8+ lymphocytes. Encouraged by the results obtained with the Cav-VP7 R0 vaccine vector, immunized animals were challenged with either the homologous BTV-2 or the heterologous BTV-8 serotype and viral burden in plasma was followed by real-time RT-PCR. The immune responses triggered by Cav-VP7 R0 were insufficient to afford protective immunity against BTV infection, despite partial protection obtained against homologous challenge. This work underscores the need to further characterize the role of BTV proteins in cross-protective immunity.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of VP7, a Bluetongue Virus Group Specific Antigen by Viral Vectors: Analysis of the Induced Immune Responses and Evaluation of Protective Potential in Sheep

et al. 2014

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“…Using successive challenge with BTV-8, we investigated the expansion of VP7-specific CD8 + and CD4 + T cells [18]. Furthermore, we studied the inflammatory response during recall responses.…”

Section: Introductionmentioning

confidence: 99%

Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Rojas

Rodríguez-Calvo

Sevilla

2017

Vet Res

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In most viral infections, recall T cell responses are critical for protection. The magnitude of these secondary responses can also affect the CD8 and CD4 epitope repertoire diversity. Bluetongue virus (BTV) infection in sheep elicits a T cell response that contributes to viremia control and could be relevant for cross-protection between BTV serotypes. Here, we characterized CD4+ and CD8+ T cell responses during primary and recall responses. During primary immune responses, both CD4+ and CD8+ T cell populations expanded by 14 days post-infection (dpi). CD4+ T cell populations showed a lower peak of expansion and prolonged contraction phase compared to CD8+ T cell populations. Recall responses to BTV challenge led to BTV-specific expansion and activation of CD8+ but not of CD4+ T cells. The evolution of the BTV-specific TCR repertoire was also characterized in response to VP7 peptide stimulation. Striking differences in repertoire development were noted over the time-course of infection. During primary responses, a broader repertoire was induced for MHC-I and MHC-II epitopes. However, during memory responses, a narrowed repertoire was activated towards a dominant motif in VP7 comprising amino acids 139–291. Monocytes were also examined, and expanded during acute infection resolution. In addition, pro-inflammatory cytokine levels increased after BTV inoculation and persisted throughout the experiment, indicative of a prolonged inflammatory state during BTV infections. These findings could have implications for vaccine design as the narrowing memory T cell repertoire induced after BTV re-infection could lead to the development of protective immunodominant TCR repertoires that differs between individual sheep.

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“…BTV-8 (Belgium/06), originally isolated from an infected calf in Belgium in 2006 (32), was used in the experiments. Inactivated BTV was prepared by incubation with freshly prepared 3 mM binary ethyleneimine (BEI) for 24 h at 37°C, and the process was stopped by adding 0.02 M sodium thiosulfate (33). Murine bone marrow cells (BMCs) were incubated for 1 h at 37°C with virus at a multiplicity of infection (MOI) of 0.1 PFU/cell at day 0 of culture, after 6 days (day 6) or after 10 days (day 10) in culture.…”

Section: Methodsmentioning

confidence: 99%

Type I Interferon Limits the Capacity of Bluetongue Virus To Infect Hematopoietic Precursors and Dendritic Cells In Vitro and In Vivo

Rodríguez-Calvo

Rojas

Martı́n

et al. 2014

J Virol

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T cell responses to bluetongue virus are directed against multiple and identical CD4+ and CD8+ T cell epitopes from the VP7 core protein in mouse and sheep

Cited by 36 publications

References 32 publications

Expression of VP7, a Bluetongue Virus Group Specific Antigen by Viral Vectors: Analysis of the Induced Immune Responses and Evaluation of Protective Potential in Sheep

Expression of VP7, a Bluetongue Virus Group Specific Antigen by Viral Vectors: Analysis of the Induced Immune Responses and Evaluation of Protective Potential in Sheep

Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Type I Interferon Limits the Capacity of Bluetongue Virus To Infect Hematopoietic Precursors and Dendritic Cells In Vitro and In Vivo

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