PLOS ONE. 2013; 8(11):e76104.

PubMed ID: 24312165

Impact of HIV-1 backbone on neutralization sensitivity: Neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone

Chenine AL, Wieczorek L, Sanders-Buell E, Wesberry M, Towle T, Pillis DM, Molnar S, McLinden R, Edmonds T, Hirsch I, O'Connell R, McCutchan FE, Montefiori DC, Ochsenbauer C, Kappes JC, Kim JH, Polonis VR, Tovanabutra S

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.