title: Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone.
abstract: Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecular clones (IMC), that i) express a reporter gene, ii) are representative of globally diverse subtypes and iii) are engineered to easily exchange envelope (env) genes for expression of sequences of interest. Thus far, a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the ectodomain of heterologous env coding sequences can be expressed has been successfully developed but as execution of HIV-1 vaccine efficacy trials shifts increasingly to non-subtype B epidemics (Southern African and Southeast Asia), non-subtype B HIV-1 reagents are needed to support vaccine development. Here we describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) that were engineered to express heterologous gp160 Envs. 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly acute, in subtype-matched and -unmatched HIV backbones were tested for functionality and neutralization sensitivity. Our results suggest a possible effect of non-env HIV-1 genes on the interaction of Env and neutralizing antibodies and highlight the need to generate a library of IMCs representative of the HIV-1 subtype spectrum to be used as standardized neutralization assay reagents for assessing HIV-1 vaccine efficacy.
authors: The Henry M. Jackson Foundation, Bethesda, Maryland, United States of America ; Military HIV Research Program, Silver Spring, Maryland, United States of America.
authors: Agnès-Laurence
authors: AL
authors: Chenine
authors: Lindsay
authors: L
authors: Wieczorek
authors: Eric
authors: E
authors: Sanders-Buell
authors: Maggie
authors: M
authors: Wesberry
authors: Teresa
authors: T
authors: Towle
authors: Devin M
authors: DM
authors: Pillis
authors: Sebastian
authors: S
authors: Molnar
authors: Robert
authors: R
authors: McLinden
authors: Tara
authors: T
authors: Edmonds
authors: Ivan
authors: I
authors: Hirsch
authors: Robert
authors: R
authors: O'Connell
authors: Francine E
authors: FE
authors: McCutchan
authors: David C
authors: DC
authors: Montefiori
authors: Christina
authors: C
authors: Ochsenbauer
authors: John C
authors: JC
authors: Kappes
authors: Jerome H
authors: JH
authors: Kim
authors: Victoria R
authors: VR
authors: Polonis
authors: Sodsai
authors: S
authors: Tovanabutra
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D019677:Artificial Gene Fusion; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D015870:Gene Expression; D023061:Gene Order; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus