Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus macaques by altering priming before adenovirus boosting

BACKGROUND: Preventive and therapeutic vaccine strategies aimed at controlling hepatitis C virus (HCV) infection should mimic the immune responses observed in patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+ cell responses to multiple antigens, including nonstructural pr...

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Authors: Rollier, C.S. (Christine S.)|||/items/a6393173-8cd1-423f-bbeb-3a3e5e4991ff, Verschoor, E.J. (Ernst J.)|||/items/186b987c-b48a-419b-b1bc-a24083ffc189, Paranhos-Baccala, G. (Glaucia)|||/items/1923d65b-b1af-4618-87ed-6e3bdd918056, Drexhage, J.A.R. (Joost A.R.)|||/items/f8bf1cb5-f676-450b-a302-dd00d2dcb742, Verstrepen, B.E. (Babs E.)|||/items/504b514f-c420-43d8-9eee-56779d12f294, Berland, J.L. (Jean-Luc)|||/items/bed7e0af-0d00-4b6b-ba54-6a1f14e36268, Himoudi, N. (Nourredine)|||/items/d25a11a4-955c-4672-bf67-adc5af934250, Barnfield, C. (Christina)|||/items/cfd1c9ad-41ff-4161-870e-e06fa0fced96, Liljestrom, P. (Peter)|||/items/605bf6bb-bad2-4c2f-8872-be9e005005d9, Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c, Ruiz, J. (Juan)|||/items/e71ee758-aef7-4ed6-b282-e483e9d9ba8e, Inchauspe, G. (Geneviese)|||/items/80d83124-595d-495b-b528-1b352e722515, Heeney, J.L. (Jonathan L.)|||/items/51bad2fe-2f76-4bf5-b8a0-14782c13a30c
Format: article
Publication Date:2005
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/21726
Online Access:https://hdl.handle.net/10171/21726
Access Level:Open access
Keyword:Hepacivirus/immunology
Hepatitis C/immunology
Immunization/methods
Viral Hepatitis Vaccines/immunology
Viral Nonstructural Proteins/immunology
Description
Summary:BACKGROUND: Preventive and therapeutic vaccine strategies aimed at controlling hepatitis C virus (HCV) infection should mimic the immune responses observed in patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+ cell responses to multiple antigens, including nonstructural protein (NS) 3. Given the experience with human immunodeficiency virus, the best candidates for this are based on DNA prime, pox, or adenovirus boost regimens. METHODS: In rhesus macaques, we compared NS3-expressing DNA prime and adenovirus boost strategy with 2 alternative priming approaches aimed at modifying Th1 and CD8+ responses: DNA adjuvanted with interleukin (IL)-2- and -12-encoding plasmids or Semliki Forest virus (SFV). RESULTS: All prime-boost regimens elicited NS3-specific B and T cell responses in rhesus macaques, including CD8+ responses. SFV priming induced higher lymphoproliferation and longer Th1 memory responses. The use of IL-2- and IL-12-expressing vectors resulted in reduced Th2 and antibody responses, which led to increased Th1 skewing but not to an increase in the magnitude of the IFN- gamma and CD8+ responses. CONCLUSIONS: All strategies induced Th1 cellular responses to HCV NS3, with fine modulations depending on the different priming approaches. When they are developed for more HCV antigens, these strategies could be beneficial in therapeutic vaccine approaches.

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