Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm.
The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC(50)) neutralization titers of >or=100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC(50) titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.
Simek
Melissa D
MD
International AIDS Vaccine Initiative, New York, NY 10028, USA. Msimek@iavi.org
Rida
Wasima
W
Priddy
Frances H
FH
Pung
Pham
P
Carrow
Emily
E
Laufer
Dagna S
DS
Lehrman
Jennifer K
JK
Boaz
Mark
M
Tarragona-Fiol
Tony
T
Miiro
George
G
Birungi
Josephine
J
Pozniak
Anton
A
McPhee
Dale A
DA
Manigart
Olivier
O
Karita
Etienne
E
Inwoley
André
A
Jaoko
Walter
W
Dehovitz
Jack
J
Bekker
Linda-Gail
LG
Pitisuttithum
Punnee
P
Paris
Robert
R
Walker
Laura M
LM
Poignard
Pascal
P
Wrin
Terri
T
Fast
Patricia E
PE
Burton
Dennis R
DR
Koff
Wayne C
WC
D000293:Adolescent; D000328:Adult; D000349:Africa / Q000453:epidemiology; D000368:Aged; D000465:Algorithms; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013785:Thailand / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
D015483:HIV Antibodies; D007074:Immunoglobulin G