Melissa D. SimekWasima RidaFrances H. PriddyPham PungEmily CarrowDagna S. LauferJennifer K. LehrmanMark BoazTony Tarragona-FiolGeorge MiiroJosephine BirungiAnton PozniakDale A. McPheeOlivier ManigartEtienne KaritaAndré InwoleyWalter JaokoJack DeHovitzLinda Gail BekkerPunnee PitisuttithumRobert ParisLaura M. WalkerPascal PoignardTerri WrinPatricia E. FastDennis R. BurtonWayne C. KoffInternational AIDS Vaccine InitiativeMonogram BiosciencesScripps Research InstituteEmory UniversityUganda Virus Research InstituteNational Center in HIV-1 Epidemiology and Clinical ResearchSt Stephen's AIDS TrustAdvanced BioadjuvantsUniversity of NairobiSUNY Downstate Medical CenterUniversity of Cape TownMahidol UniversityArmed Forces Research Institute of Medical Sciences, ThailandImperial College LondonSanofi Pasteur2018-09-132018-09-132009-07-01Journal of Virology. Vol.83, No.14 (2009), 7337-73480022538X2-s2.0-67650453747https://repository.li.mahidol.ac.th/handle/20.500.14594/27694The 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 (IC50) neutralization titers of > 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 IC50 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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.Mahidol UniversityImmunology and MicrobiologyHuman 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 algorithmArticleSCOPUS10.1128/JVI.00110-09