Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2

Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8+ T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus–specific CD8+ T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon γ, interleukin 2, macrophage inflammatory protein 1β, and tumor necrosis factor α after antigenic stimulation. Responding CD8+ T cells exhibited an unusual phenotype (CD45RO−CD27intermediate). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8+ T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.

Download Full-text

Insertion of interleukin-2 (IL-2) and interleukin-12 (IL-12) genes into vaccinia virus results in effective anti-tumor responses without toxicity

Vaccine ◽

10.1016/s0264-410x(02)00032-4 ◽

2002 ◽

Vol 20 (13-14) ◽

pp. 1862-1869 ◽

Cited By ~ 31

Author(s):

Howard L Kaufman ◽

Ken Flanagan ◽

Christopher S.D Lee ◽

Donato J Perretta ◽

Heidi Horig

Keyword(s):

Vaccinia Virus ◽

Interleukin 2 ◽

Interleukin 12

Download Full-text

Expansion and Exhaustion of T-Cell Responses during Mutational Escape from Long-Term Viral Control in Two DNA/Modified Vaccinia Virus Ankara-Vaccinated and Simian-Human Immunodeficiency Virus SHIV-89.6P-Challenged Macaques

Journal of Virology ◽

10.1128/jvi.02242-07 ◽

2008 ◽

Vol 82 (8) ◽

pp. 4149-4153 ◽

Cited By ~ 10

Author(s):

Shanmugalakshmi Sadagopal ◽

Rama Rao Amara ◽

Sunil Kannanganat ◽

Sunita Sharma ◽

Lakshmi Chennareddi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Vaccinia Virus ◽

Interleukin 2 ◽

Initial Increase ◽

Viral Control ◽

Modified Vaccinia Virus Ankara ◽

Immunodeficiency Virus ◽

Ifn Γ

ABSTRACT In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 and CD8 T cells in 2 of 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control of a simian-human immunodeficiency virus 89.6P challenge by 196 weeks postchallenge. Our results show that both mutation and exhaustion contributed to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase and then loss of breadth and frequency. Antiviral gamma interferon (IFN-γ)- and interleukin 2-coproducing cells were lost before IFN-γ-producing cells and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long-term control contained mutations.

Download Full-text