Sustained suppression of SHIV89.6P replication in macaques by vaccine-induced CD8+ memory T cells.
OBJECTIVE
We previously demonstrated that a strategy of co-immunizing cynomologous macaques with a simian/human immunodeficiency virus DNA-based vaccine and a plasmid encoding macaque interleukin (IL)-15 induces a strong CD8 and CD4 effector T-cell response that, upon subsequent challenge with SHIV89.6P, controls viral replication and protects immunized animals against ongoing infection. In this follow-up study, we measured viral replication 2 years after vaccination challenge and determined the mechanism by which antigen-specific CD8 T cells suppress viral replication.


METHODS
From the original group of 18, we assessed the immune response in the 13 surviving animals. In addition, using cM-T807, we depleted CD8 lymphocytes to assess the role CD8 cells play in suppression of viral replication.


RESULTS
We found that peripheral blood mononuclear cells from vaccinated animals had a robust simian immunodeficiency virus Gag-specific IFN-gamma response. In addition, in the DNA and IL-15 group, we observed higher levels of simian immunodeficiency virus Gag-specific, proliferating CD8 T cells. The profile of these cells revealed more central memory than effector cells. When we transiently depleted animals of CD8 T cells, plasma viral load increased, and peak viral load was lower in the DNA and IL-15 group compared with the DNA alone and control groups. As CD8 T cells recovered, viral replication was controlled and we observed an increase in the number of antigen-specific effector CD8 T cells.


CONCLUSIONS
We conclude that co-immunization with a simian/human immunodeficiency virus DNA-based vaccine and IL-15 achieves sustained viral suppression and that vaccine-induced CD8 memory T cells, which differentiate into effector cells, are central to that suppression.
Yin
Jiangmei
J
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Dai
Anlan
A
Kutzler
Michele A
MA
Shen
Anding
A
Lecureux
Jonathan
J
Lewis
Mark G
MG
Waldmann
Thomas
T
Weiner
David B
DB
Boyer
Jean D
JD