LL-37 antimicrobial peptide and heterologous prime-boost vaccination regimen significantly induce HIV-1 Nef-Vpr antigen- and virion-specific immune responses in mice.
Nikyar. Arash A; Bolhassani. Azam A; Agi. Elnaz E
Key Findings
- LL-37 acts as a cell‑penetrating carrier that boosts DNA vaccine effectiveness in mice
- A heterologous DNA‑prime/ protein‑boost regimen with LL-37 and Montanide 720 generates higher IgG2a, IFN‑γ and Granzyme B responses
- Low‑dose DNA (5 µg) with LL-37 outperforms high‑dose naked DNA (50 µg)
Practical Outcomes
- For now, the findings are mainly of interest to vaccine researchers. They suggest LL-37 could be explored as a delivery tool in future human vaccines, but there’s no safe, proven protocol for self‑administration or direct health‑hacking use yet.
Summary
Scientists tested a tiny protein called LL-37 as a carrier to help DNA vaccines work better in mice. They found that using LL-37 with a DNA vaccine and a protein boost gave stronger immune responses than DNA alone, even at a lower DNA dose. This work is still early‑stage animal research and not a ready‑to‑use method for people.
Abstract
HIV infection still remains a leading cause of morbidity and mortality worldwide. The inability of highly-active antiretroviral therapy in HIV-1 eradication led to development of therapeutic vaccines. Exploiting effective immunogenic constructs and potent delivery systems are important to generate effective therapeutic vaccines, and overcome their poor membrane permeability. Among HIV-1 proteins, the Nef and Vpr proteins can be considered as antigen candidates in vaccine design. In this study, the immunogenicity of Nef-Vpr antigen candidate in different regimens along with antimicrobial peptide LL-37 (as a DNA carrier) and Montanide 720 (as an adjuvant) was studied in mice. Moreover, the secretion of cytokines was assessed in virion-exposed mice lymphocytes in vitro. Our data indicated that groups immunized with the homologous protein + Montanide regimen (group 1), and also the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) could significantly generate strong immune responses as compared to groups immunized with the DNA constructs (groups 3 & 4). Moreover, immunization of mice with the homologous DNA + LL-37 regimen in low dose of DNA (5 µg) could induce higher immune responses than the homologous naked DNA regimen in high dose of DNA (50 µg) indicating the role of LL-37 as a cell penetrating peptide. Additionally, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) induced significantly IFN-gamma secretion from virion-exposed lymphocytes in vitro. Generally, the use of LL-37 for DNA delivery, Montanide 720 as an adjuvant, and heterologous DNA prime/protein boost strategy could significantly increase IgG2a, IFN-gamma, and Granzyme B, and maintain cytokine secretion after exposure to virions. Indeed, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen can be considered as a potent strategy for development of therapeutic HIV vaccines.
Study Information
pubmed
2022
2022-12-22T00:00:00.000Z
10.1007/s10529-022-03339-7
3
45