title: Novel approach for differential diagnosis of HIV infections in the face of vaccine-generated antibodies: utility for detection of diverse HIV-1 subtypes.
abstract: Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from >3,000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
authors.forename: Surender
authors.initials: S
authors.lastname: Khurana
authors.forename: James
authors.initials: J
authors.lastname: Needham
authors.forename: Susan
authors.initials: S
authors.lastname: Park
authors.forename: Bonnie
authors.initials: B
authors.lastname: Mathieson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: George
authors.initials: G
authors.lastname: Nemo
authors.forename: Phillipe
authors.initials: P
authors.lastname: Nyambi
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Suman
authors.initials: S
authors.lastname: Laal
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: James
authors.initials: J
authors.lastname: McIntyre
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
authors.forename: Sherwin
authors.initials: S
authors.lastname: Lee
authors.forename: Shixing
authors.initials: S
authors.lastname: Tang
authors.forename: Elliot
authors.initials: E
authors.lastname: Cowan
authors.forename: Chris
authors.initials: C
authors.lastname: Beyrer
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Anatole
authors.initials: A
authors.lastname: Tounkara
authors.forename: Ousmane
authors.initials: O
authors.lastname: Koita
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.forename: Nga
authors.initials: N
authors.lastname: Nguyen
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Deborah
authors.initials: D
authors.lastname: Todd
authors.forename: Peter
authors.initials: P
authors.lastname: Mugenyi
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.forename: Eduard
authors.initials: E
authors.lastname: Sanders
authors.forename: Nzeera
authors.initials: N
authors.lastname: Ketter
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
mesh_terms: D015492:AIDS Serodiagnosis / Q000379:methods*; D016915:AIDS Vaccines / Q000276:immunology*; D003429:Cross Reactions; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology; D006801:Humans; D019151:Peptide Library; D012680:Sensitivity and Specificity
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D019151:Peptide Library