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Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor.

Ren, H, Ferguson, BJ, Maluquer de Motes, C, Sumner, RP, Harman, LE and Smith, GL (2015) Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor. Immunology, 145 (1). pp. 34-49.

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Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8(+) T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8(+) T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8(+) T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Ren, H
Ferguson, BJ
Maluquer de Motes,
Sumner, RP
Harman, LE
Smith, GL
Date : May 2015
DOI : 10.1111/imm.12422
Uncontrolled Keywords : CD8+ T-cell memory, N1L gene, nuclear factor-κB inhibitor, vaccination, vaccinia virus, Animals, CD8-Positive T-Lymphocytes, Cell Proliferation, Female, Immunologic Memory, Mice, Mutation, Missense, NF-kappa B, Vaccinia, Vaccinia virus, Viral Proteins, Viral Vaccines
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:27
Last Modified : 24 Jan 2020 19:20

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