TY - JOUR

T1 - The effects of high shear rates on the average hydrodynamic diameter measured in biomimetic HIV Gag virus-like particle dispersions

AU - Wolf, Tobias

AU - Calisan, Kerim Kadir

AU - Stitz, Jörn

AU - Barbe, Stéphan

N1 - Publisher Copyright: Copyright © 2024 Wolf, Calisan, Stitz and Barbe.

PY - 2024/5/27

Y1 - 2024/5/27

N2 - HIV Gag virus-like particles (HIV Gag VLPs) are promising HIV vaccine candidates. In the literature, they are often described as shear-sensitive particles, and authors usually recommend the operation of tangential flow filtration (TFF) gently at shear rates below 4,000 s−1 to 6,000 s−1. This in turn poses a severe limitation to the performance of TFF-mediated concentration of VLPs, which would be substantially enhanced by working at higher shear rates. To our knowledge, studies examining the shear sensitivity of HIV Gag VLPs and providing detailed information and evidence for the fragility of these particles have not been conducted yet. Thus, we investigated the effect of high shear rates on the colloidal stability of mosaic VLPs (Mos-VLPs) as relevant examples for HIV Gag VLPs. For this purpose, Mos-VLPs were exposed to different shear rates ranging from 3,395 s−1 to 22, 365 s−1 for 2 h. The average hydrodynamic diameter (AHD) and the polydispersity index (PDI) of the associated particle size distribution were used as stability indicators and measured after the treatment and during storage through dynamic light scattering. At high shear rates, we observed an increase in both AHD and PDI during the storage of HIV Mos1.Gag VLPs (bVLP—without envelope proteins) and Mos1.Gag + Mos2S.Env VLPs (eVLP—with envelope proteins). eVLPs exhibited higher colloidal stability than bVLPs, and we discuss the potential stabilizing role of envelope proteins. We finally demonstrated that the dispersion medium also has a considerable impact on the stability of Mos-VLPs.

AB - HIV Gag virus-like particles (HIV Gag VLPs) are promising HIV vaccine candidates. In the literature, they are often described as shear-sensitive particles, and authors usually recommend the operation of tangential flow filtration (TFF) gently at shear rates below 4,000 s−1 to 6,000 s−1. This in turn poses a severe limitation to the performance of TFF-mediated concentration of VLPs, which would be substantially enhanced by working at higher shear rates. To our knowledge, studies examining the shear sensitivity of HIV Gag VLPs and providing detailed information and evidence for the fragility of these particles have not been conducted yet. Thus, we investigated the effect of high shear rates on the colloidal stability of mosaic VLPs (Mos-VLPs) as relevant examples for HIV Gag VLPs. For this purpose, Mos-VLPs were exposed to different shear rates ranging from 3,395 s−1 to 22, 365 s−1 for 2 h. The average hydrodynamic diameter (AHD) and the polydispersity index (PDI) of the associated particle size distribution were used as stability indicators and measured after the treatment and during storage through dynamic light scattering. At high shear rates, we observed an increase in both AHD and PDI during the storage of HIV Mos1.Gag VLPs (bVLP—without envelope proteins) and Mos1.Gag + Mos2S.Env VLPs (eVLP—with envelope proteins). eVLPs exhibited higher colloidal stability than bVLPs, and we discuss the potential stabilizing role of envelope proteins. We finally demonstrated that the dispersion medium also has a considerable impact on the stability of Mos-VLPs.

KW - HIV Gag virus-like particles

KW - HIV vaccines

KW - hydrodynamic diameter

KW - mosaic virus-like particles

KW - shear rate stability

KW - shear-induced aggregation

KW - virus-like particles

UR - http://www.scopus.com/inward/record.url?scp=85195584545&partnerID=8YFLogxK

U2 - 10.3389/fbioe.2024.1367405

DO - 10.3389/fbioe.2024.1367405

M3 - Article

AN - SCOPUS:85195584545

VL - 12

JO - Frontiers in Bioengineering and Biotechnology

JF - Frontiers in Bioengineering and Biotechnology

SN - 2296-4185

M1 - 1367405

ER -