Immunisation with the membrane proximal external region of gp41 of HIV-1 grafted into the transmembrane envelope protein of a gammaretrovirus

Abstract

Background Immunisation with the transmembrane envelope (TM) proteins p15E of different gammaretroviruses (e.g., porcine endogenous retrovirus, feline leukaemia virus, Koala retrovirus) resulted in strong neutralising activity, the antibodies recognised epitopes in the fusion peptide proximal region (FPPR) and in the membrane proximal external region (MPER). The MPER epitopes were localised similarly as the epitopes recognised by the broadly neutralising antibodies 2F5 and 4E10 in gp41 of HIV-1. Despite the evolutionary difference between HIV-1 and the gammaretroviruses, the MPER epitope of antibodies neutralising PERV (FEGWFN) showed partial homology to the epitope of the 4E10 (NWFNIT, note three identical amino acids). To generate hybrid antigens able to induce 2F5/4E10-like antibodies, sequences of the MPER and FPPR of gp41 were grafted into the p15E backbone of a gammaretrovirus.