The Effects of High Shear Rates on the Average Hydrodynamic Diameter Measured in Biomimetic HIV Gag Virus-like Particle Dispersions

Overview

Journal Front Bioeng Biotechnol

Date 2024 Jun 11

PMID 38860137

Authors

Tobias Wolf

Kerim Kadir Calisan

Jorn Stitz

Stephan Barbe

Affiliations

Soon will be listed here.

Abstract

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 to 6,000 s. 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 to 22, 365 s 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 VLPs (bVLP-without envelope proteins) and 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.

References

Paliard X, Liu Y, Wagner R, Wolf H, Baenziger J, Walker C . Priming of strong, broad, and long-lived HIV type 1 p55gag-specific CD8+ cytotoxic T cells after administration of a virus-like particle vaccine in rhesus macaques. AIDS Res Hum Retroviruses. 2000; 16(3):273-82. DOI: 10.1089/088922200309368. View

Rosengarten J, Schatz S, Wolf T, Barbe S, Stitz J . Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes. Virology. 2022; 568:41-48. DOI: 10.1016/j.virol.2022.01.008. View

Goepfert P, Elizaga M, Seaton K, Tomaras G, Montefiori D, Sato A . Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2014; 210(1):99-110. PMC: 4072895. DOI: 10.1093/infdis/jiu003. View

Pitoiset F, Vazquez T, Levacher B, Nehar-Belaid D, Derian N, Vigneron J . Retrovirus-Based Virus-Like Particle Immunogenicity and Its Modulation by Toll-Like Receptor Activation. J Virol. 2017; 91(21). PMC: 5640832. DOI: 10.1128/JVI.01230-17. View

Zhang S, Cubas R, Li M, Chen C, Yao Q . Virus-like particle vaccine activates conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells. Mol Immunol. 2009; 46(10):1988-2001. PMC: 2702656. DOI: 10.1016/j.molimm.2009.03.008. View

Ladd Effio C, Hubbuch J . Next generation vaccines and vectors: Designing downstream processes for recombinant protein-based virus-like particles. Biotechnol J. 2015; 10(5):715-27. DOI: 10.1002/biot.201400392. View

Ding C, Patel D, Ma Y, Mann J, Wu J, Gao Y . Employing Broadly Neutralizing Antibodies as a Human Immunodeficiency Virus Prophylactic & Therapeutic Application. Front Immunol. 2021; 12:697683. PMC: 8329590. DOI: 10.3389/fimmu.2021.697683. View

Barouch D, OBrien K, Simmons N, King S, Abbink P, Maxfield L . Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med. 2010; 16(3):319-23. PMC: 2834868. DOI: 10.1038/nm.2089. View

Nooraei S, Bahrulolum H, Hoseini Z, Katalani C, Hajizade A, Easton A . Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnology. 2021; 19(1):59. PMC: 7905985. DOI: 10.1186/s12951-021-00806-7. View

10.

Negrete A, Pai A, Shiloach J . Use of hollow fiber tangential flow filtration for the recovery and concentration of HIV virus-like particles produced in insect cells. J Virol Methods. 2013; 195:240-6. DOI: 10.1016/j.jviromet.2013.10.017. View

11.

Bachmann M, Rohrer U, Kundig T, Burki K, Hengartner H, Zinkernagel R . The influence of antigen organization on B cell responsiveness. Science. 1993; 262(5138):1448-51. DOI: 10.1126/science.8248784. View

12.

Lorenzo E, Miranda L, Godia F, Cervera L . Downstream process design for Gag HIV-1 based virus-like particles. Biotechnol Bioeng. 2023; 120(9):2672-2684. DOI: 10.1002/bit.28419. View

13.

Ndungu T, Weiss R . On HIV diversity. AIDS. 2012; 26(10):1255-60. DOI: 10.1097/QAD.0b013e32835461b5. View

14.

Tsunetsugu-Yokota Y, Morikawa Y, Isogai M, Kawana-Tachikawa A, Odawara T, Nakamura T . Yeast-derived human immunodeficiency virus type 1 p55(gag) virus-like particles activate dendritic cells (DCs) and induce perforin expression in Gag-specific CD8(+) T cells by cross-presentation of DCs. J Virol. 2003; 77(19):10250-9. PMC: 228384. DOI: 10.1128/jvi.77.19.10250-10259.2003. View

15.

Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D . Diversity considerations in HIV-1 vaccine selection. Science. 2002; 296(5577):2354-60. DOI: 10.1126/science.1070441. View

16.

Zolla-Pazner S, deCamp A, B Gilbert P, Williams C, Yates N, Williams W . Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS One. 2014; 9(2):e87572. PMC: 3913641. DOI: 10.1371/journal.pone.0087572. View

17.

Nabi G, Storcksdieck Genannt Bonsmann M, Tenbusch M, Gardt O, Barouch D, Temchura V . GagPol-specific CD4⁺ T-cells increase the antibody response to Env by intrastructural help. Retrovirology. 2013; 10:117. PMC: 3874777. DOI: 10.1186/1742-4690-10-117. View

18.

Baden L, Stieh D, Sarnecki M, Walsh S, Tomaras G, Kublin J . Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study. Lancet HIV. 2020; 7(10):e688-e698. PMC: 7529856. DOI: 10.1016/S2352-3018(20)30229-0. View

19.

Collins D, Gaiha G, Walker B . CD8 T cells in HIV control, cure and prevention. Nat Rev Immunol. 2020; 20(8):471-482. PMC: 7222980. DOI: 10.1038/s41577-020-0274-9. View

20.

Temchura V, Kalinin S, Nabi G, Tippler B, Niezold T, Uberla K . Divergence of primary cognate B- and T-cell proliferative responses to subcutaneous and intravenous immunization with virus-like particles. Viruses. 2014; 6(8):3334-47. PMC: 4147698. DOI: 10.3390/v6083334. View