Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes

• DOI: 10.1128/jvi.02827-12
• Publication Date: 2013-03-07T04:12:55Z
• Authors: Simon Hoffenberg; Rebecca Powell; Alexei Carpov; Denise Wagner; Aaron Wilson; Sergei Kosakovsky...; Ross Lindsay; Heather Arendt; Joanne DeStefano; Sanjay Phogat; Pascal Poignard; Steven P. Fling; Melissa Simek; Celia LaBranche; David Montefiori; Terri Wrin; Pham Phung; Dennis Burton; Wayne Koff; C. Richter King; Christopher L. Parks; Michael J. Caulfield
• Keywords: Antigenicity; AIDS Vaccines

Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both are highly potent neutralize greater than 70% of viruses tested. We sought to begin immunogen design based on viral sequences this patient; however, pseudoviruses prepared 19 envelope resistant neutralization by PG16. Therefore, we used a bioinformatics approach identify closely related that potentially sensitive A most-recent common ancestor (MRCA) sequence for the (Env) was determined aligned 99 subtype gp160 Los Alamos HIV database. Virus BG505.W6M.ENV.C2 (BG505) found have highest degree homology (73%) MRCA sequence. Pseudoviruses Env broad panel bNAbs, including When expressed 293T cells as soluble gp120, BG505 monomer bound well both further showed point mutation (L111A) enabled more efficient production stable gp120 preserves major epitopes. Finally, adjuvanted formulation protein elicited in rabbits (following DNA vaccine prime) antisera competed bNAbs 3 classes nonoverlapping Thus, warrants investigation candidate, stand-alone protein, or component vector.