Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.
Barouch
D H
DH
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. dan_barouch@hotmail.com
Santra
S
S
Schmitz
J E
JE
Kuroda
M J
MJ
Fu
T M
TM
Wagner
W
W
Bilska
M
M
Craiu
A
A
Zheng
X X
XX
Krivulka
G R
GR
Beaudry
K
K
Lifton
M A
MA
Nickerson
C E
CE
Trigona
W L
WL
Punt
K
K
Freed
D C
DC
Guan
L
L
Dubey
S
S
Casimiro
D
D
Simon
A
A
Davies
M E
ME
Chastain
M
M
Strom
T B
TB
Gelman
R S
RS
Montefiori
D C
DC
Lewis
M G
MG
Emini
E A
EA
Shiver
J W
JW
Letvin
N L
NL
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000628:therapy / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015483:HIV Antibodies; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA