Liposome-based peptide vaccines to elicit immune responses against the membrane active domains of the HIV-1 Env glycoprotein

The fusion peptide (FP) and the Trp-rich membrane proximal external region (MPER) display membrane activity during HIV-1 fusion. These domains are highly conserved in the envelope glycoprotein (Env) and, consequently, antibodies targeting these regions block entry of divergent HIV strains and isolates into target cells. With the aim of recovering concurrent responses against the membrane-active Env domains, we have produced hybrid peptides that connect FP and MPER sequences via flexible aminohexanoic acid tethers, and tested their potential as immunogens. We demonstrate that liposome-based formulations containing FP-MPER hybrid peptides could elicit in rabbits, antibodies with the binding sequence specificity of neutralizing antibodies that engage with the N-terminal MPER sub-region. Determination of the thermodynamic parameters of binding using the Fab 2F5 as an N-terminal MPER antibody model, revealed that the hydrophobic interaction surface for epitope engagement appears to be optimal in the FP-MPER hybrid. In general, our data support: i) the use of liposomes as carriers for membrane active peptides; ii) the capacity of these liposome-based vaccines to focus humoral responses to Nterminal MPER epitopes; and iii) the need to include lipid membranes in immunogens to elicit such specific responses.

Automated summary

This study investigates the role of fusion peptide and Trp-rich membrane proximal external region in HIV-1 fusion and demonstrates that liposome-based formulations containing FP-MPER hybrid peptides can induce the production of specific neutralizing antibodies in rabbits. The results support the use of liposomes as vaccine carriers and the inclusion of lipid membranes in immunogens to elicit specific humoral responses.