Engineered ClearColi™-derived outer membrane vesicles as functional carriers for development of HIV-1 therapeutic vaccine candidate.

Autor: Sadeghi L; Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran., Bolhassani A; Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran. Electronic address: azam.bolhassani@yahoo.com., Mohit E; Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: el_mohit@yahoo.com., Baesi K; Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran., Aghasadeghi MR; Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran., Milani A; Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran., Agi E; Iranian Comprehensive Hemophilia Care Center, Tehran, Iran.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2024 Aug; Vol. 193, pp. 106749. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1016/j.micpath.2024.106749
Abstrakt: Bacteria-derived outer membrane vesicles (OMVs) can be engineered to incorporate foreign antigens. This study explored the potential of ClearColi™-derived OMVs as a natural adjuvant and a carrier (recombinant OMVs or rOMVs) for development of an innovative therapeutic vaccine candidate harboring HIV-1 Nef and Nef-Tat antigens. Herein, the rOMVs containing CytolysinA (ClyA)-Nef and ClyA-Nef-Tat fusion proteins were isolated from ClearColi™ strain. The presence of Nef and Nef-Tat proteins on their surface (rOMV Nef and rOMV Nef-Tat ) was confirmed by western blotting after proteinase K treatment. Immune responses induced by Nef and Nef-Tat proteins emulsified with Montanide® ISA720 or mixed with OMVs, and also rOMV Nef and rOMV Nef-Tat were investigated in BALB/c mice. Additionally, the potency of splenocytes exposed to single-cycle replicable (SCR) HIV-1 virions was assessed for the secretion of cytokines in vitro. Our findings showed that the rOMVs as an antigen carrier (rOMV Nef and rOMV Nef-Tat ) induced higher levels of IgG2a, IFN-γ and granzyme B compared to OMVs as an adjuvant (Nef + OMV and Nef-Tat + OMV), and also Montanide® ISA720 (Nef + Montanide and Nef-Tat + Montanide). Moreover, IFN-γ level in splenocytes isolated from mice immunized with rOMV Nef-Tat was higher than other regimens after exposure to SCR virions. Generally, ClearColi™-derived rOMVs can serve as potent carriers for developing effective vaccines against HIV-1 infection.
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 © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: