Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment

Abstract

The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB 409–505 and gD 301–309 , selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 ⋅ 10 −7 mol ⋅ Kg −1 ; hydrodynamic radii (R H ) between 50–80 nm, and a zeta potential (ζ) around − 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 μM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.

Self-assembling peptide-based building blocks in medical applications

“…KLIP) was necessary; the self-assembled nanostructures were sufficient to induce humoral immunity in vivo , while the peptide co-delivered with an unloaded micelle was not. Similar self-adjuvant results for PA vaccines have been shown against Herpes simplex virus (HSV) in vitro [188]. …”

Micellar Drug Delivery Systems Based on Natural Biopolymers

“…The peptide amphiphile micelles (PAMs) boost peptide-specific immune responses without causing any undesirable side effects. In the study of Accardo et al [ 124 ], PAMs were prepared and used as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection. Pure and mixed micelles, based on epitopes gB 498−505 (H-L-Ser-Ser-Ile-Glu-Phe-Ala-Arg-Leu-Amide) and gD 301−309 (H-L-Ser-Ala-Leu-Leu-Glu-Asp-Pro-Val-Gly-Amide), which were selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), were prepared by solid phase methods.…”