Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope

• Main Authors: Andrey P. Rudometov, Anton N. Chikaev, Nadezhda B. Rudometova, Denis V. Antonets, Alexander A. Lomzov, Olga N. Kaplina, Alexander A. Ilyichev, Larisa I. Karpenko
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Vaccines
• Subjects: artificial protein; polyepitope B- and T-cell HIV-1 immunogen; epitopes of broadly neutralizing HIV-1 antibodies; peptide mimic of discontinuous epitope; immunogenicity
• Online Access: https://www.mdpi.com/2076-393X/7/3/83

The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties.