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

Autor: Rujas E; Instituto Biofisika (CSIC, UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), PO Box 644, 48080 Bilbao, Spain. Electronic address: edurne.rujas@ehu.eus., Apellániz B; Department of Physiology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad, 7, 01006 Vitoria-Gasteiz, Spain; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, 01006 Vitoria-Gasteiz, Spain., Torralba J; Instituto Biofisika (CSIC, UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), PO Box 644, 48080 Bilbao, Spain., Andreu D; Laboratory of Proteomics and Protein Chemistry, Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, Spain., Caaveiro JMM; Laboratory of Global Healthcare, School of Pharmaceutical Sciences, Kyushu University, Fukuoka 819-0395, Japan., Wang S; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States of America., Lu S; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States of America., Nieva JL; Instituto Biofisika (CSIC, UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), PO Box 644, 48080 Bilbao, Spain. Electronic address: joseluis.nieva@ehu.eus.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2024 Jan; Vol. 1866 (1), pp. 184235. Date of Electronic Publication: 2023 Oct 02.
DOI: 10.1016/j.bbamem.2023.184235
Abstrakt: 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 N-terminal MPER epitopes; and iii) the need to include lipid membranes in immunogens to elicit such specific responses.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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