Magnitude and diversity of cytotoxic-T-lymphocyte responses elicited by multiepitope DNA vaccination in rhesus monkeys.
In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virus gag DNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.
Subbramanian
Ramu A
RA
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Research East-RE 113, 330 Brookline Avenue, Boston, MA 02215, USA.
Kuroda
Marcelo J
MJ
Charini
William A
WA
Barouch
Dan H
DH
Costantino
Cristina
C
Santra
Sampa
S
Schmitz
Jörn E
JE
Martin
Kristi L
KL
Lifton
Michelle A
MA
Gorgone
Darci A
DA
Shiver
John W
JW
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010957:Plasmids; D018449:SAIDS Vaccines / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D018449:SAIDS Vaccines; D019444:Vaccines, DNA