Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice.
The ubiquitous Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is etiologically linked to the development of several malignancies and autoimmune diseases. EBV has a multifaceted life cycle that comprises virus lytic replication and latency programs. Considering EBV infe...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007464 |
| _version_ | 1818901882018463744 |
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| author | Dwain G van Zyl Ming-Han Tsai Anatoliy Shumilov Viktor Schneidt Rémy Poirey Bettina Schlehe Herbert Fluhr Josef Mautner Henri-Jacques Delecluse |
| author_facet | Dwain G van Zyl Ming-Han Tsai Anatoliy Shumilov Viktor Schneidt Rémy Poirey Bettina Schlehe Herbert Fluhr Josef Mautner Henri-Jacques Delecluse |
| author_sort | Dwain G van Zyl |
| collection | DOAJ |
| description | The ubiquitous Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is etiologically linked to the development of several malignancies and autoimmune diseases. EBV has a multifaceted life cycle that comprises virus lytic replication and latency programs. Considering EBV infection holistically, we rationalized that prophylactic EBV vaccines should ideally prime the immune system against lytic and latent proteins. To this end, we generated highly immunogenic particles that contain antigens from both these cycles. In addition to stimulating EBV-specific T cells that recognize lytic or latent proteins, we show that the immunogenic particles enable the ex vivo expansion of cytolytic EBV-specific T cells that efficiently control EBV-infected B cells, preventing their outgrowth. Lastly, we show that immunogenic particles containing the latent protein EBNA1 afford significant protection against wild-type EBV in a humanized mouse model. Vaccines that include antigens which predominate throughout the EBV life cycle are likely to enhance their ability to protect against EBV infection. |
| first_indexed | 2024-12-19T20:26:48Z |
| format | Article |
| id | doaj.art-aa960ab89af049b38b5a3f0bcec6186f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-19T20:26:48Z |
| publishDate | 2018-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-aa960ab89af049b38b5a3f0bcec6186f2022-12-21T20:06:49ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-12-011412e100746410.1371/journal.ppat.1007464Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice.Dwain G van ZylMing-Han TsaiAnatoliy ShumilovViktor SchneidtRémy PoireyBettina SchleheHerbert FluhrJosef MautnerHenri-Jacques DelecluseThe ubiquitous Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is etiologically linked to the development of several malignancies and autoimmune diseases. EBV has a multifaceted life cycle that comprises virus lytic replication and latency programs. Considering EBV infection holistically, we rationalized that prophylactic EBV vaccines should ideally prime the immune system against lytic and latent proteins. To this end, we generated highly immunogenic particles that contain antigens from both these cycles. In addition to stimulating EBV-specific T cells that recognize lytic or latent proteins, we show that the immunogenic particles enable the ex vivo expansion of cytolytic EBV-specific T cells that efficiently control EBV-infected B cells, preventing their outgrowth. Lastly, we show that immunogenic particles containing the latent protein EBNA1 afford significant protection against wild-type EBV in a humanized mouse model. Vaccines that include antigens which predominate throughout the EBV life cycle are likely to enhance their ability to protect against EBV infection.https://doi.org/10.1371/journal.ppat.1007464 |
| spellingShingle | Dwain G van Zyl Ming-Han Tsai Anatoliy Shumilov Viktor Schneidt Rémy Poirey Bettina Schlehe Herbert Fluhr Josef Mautner Henri-Jacques Delecluse Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. PLoS Pathogens |
| title | Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. |
| title_full | Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. |
| title_fullStr | Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. |
| title_full_unstemmed | Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. |
| title_short | Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. |
| title_sort | immunogenic particles with a broad antigenic spectrum stimulate cytolytic t cells and offer increased protection against ebv infection ex vivo and in mice |
| url | https://doi.org/10.1371/journal.ppat.1007464 |
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