Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes.
The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.
Chen
X
X
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
Scala
G
G
Quinto
I
I
Liu
W
W
Chun
T W
TW
Justement
J S
JS
Cohen
O J
OJ
vanCott
T C
TC
Iwanicki
M
M
Lewis
M G
MG
Greenhouse
J
J
Barry
T
T
Venzon
D
D
Fauci
A S
AS
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000008:administration & dosage / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D019151:Peptide Library; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D019151:Peptide Library; D018449:SAIDS Vaccines