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Enhancement of CD 8 + T‐cell memory by removal of a vaccinia virus nuclear factor‐ κ B inhibitor
Author(s) -
Ren Hongwei,
Ferguson Brian J.,
Motes Carlos Maluquer,
Sumner Rebecca P.,
Harman Laura E. R,
Smith Geoffrey L.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12422
Subject(s) - vaccinia , cd8 , biology , cytotoxic t cell , virology , virus , immunogenicity , t cell , immunology , antibody , immune system , gene , in vitro , genetics , recombinant dna
Summary 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‐ κ B (NF‐ κ B) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (v N 1.I6E) that abrogates its inhibition of NF‐ κ B 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 v N 1.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 (v N 1.WT). This demonstrates the importance of NF‐ κ B 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.