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...

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Bibliographic Details
Published in:PLoS pathogens 2018-12, Vol.14 (12), p.e1007464-e1007464
Main Authors: van Zyl, Dwain G, Tsai, Ming-Han, Shumilov, Anatoliy, Schneidt, Viktor, Poirey, Rémy, Schlehe, Bettina, Fluhr, Herbert, Mautner, Josef, Delecluse, Henri-Jacques
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Viral - immunology
Artificial chromosomes
Autoimmune diseases
Biology and Life Sciences
Cancer
Control
Deoxyribonucleic acid
DNA
Epstein-Barr virus
Epstein-Barr virus diseases
Epstein-Barr Virus Infections - immunology
Etiology
Glycoproteins
Herpesvirus 4, Human - immunology
Herpesvirus Vaccines - immunology
Human health and pathology
Immune system
Immunogenicity
Immunology
Immunotherapy
Infections
Infectious diseases
Infectious mononucleosis
Laboratory rats
Latency
Life cycles
Life Sciences
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Medical research
Medicine and Health Sciences
Mice
Mononucleosis
Prevention
Proteins
Research and Analysis Methods
Risk factors
T cells
T-Lymphocytes, Cytotoxic - immunology
Vaccines
Viral vaccines
Virus Latency
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1007464