Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes

Rosengarten, Jamila Franca; Schatz, Stefanie; Wolf, Tobias; Barbe, Stéphan; Stitz, Jörn

doi:10.1016/j.virol.2022.01.008

Cited by 13 publications

(25 citation statements)

References 66 publications

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“…The present study demonstrated the distinct and quantitative validation of a dynamic metabolic model used to simulate fed-batch cultivation of an HIV Gag-VLP-producing HEK293 cell line. The model is based on previous work on CHO DG44 cells [19,42,47] and was adapted to the specificities of the cells used here [19,37,48]. By applying distinct and quantitative statistical methods [40], the model was shown to predict the cultivation progression of HEK293 cells accurately and precisely with regard to experimental data.…”

Section: Discussionmentioning

confidence: 99%

Towards Autonomous Process Control—Digital Twin for HIV-Gag VLP Production in HEK293 Cells Using a Dynamic Metabolic Model

et al. 2022

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Despite intensive research over the last three decades, it has not yet been possible to bring an effective vaccine against human immunodeficiency virus (HIV) and the resulting acquired immunodeficiency syndrome (AIDS) to market. Virus-like particles (VLP) are a promising approach for efficient and effective vaccination and could play an important role in the fight against HIV. For example, HEK293 (human embryo kidney) cells can be used to produce virus-like particles. In this context, given the quality-by-design (QbD) concept for manufacturing, a digital twin is of great importance for the production of HIV-Gag-formed VLPs. In this work, a dynamic metabolic model for the production of HIV-Gag VLPs was developed and validated. The model can represent the VLP production as well as the consumption or formation of all important substrates and metabolites. Thus, in combination with already described process analytical technology (PAT) methods, the final step towards the implementation of a digital twin for process development and design, as well as process automation, was completed.

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Section: Discussionmentioning

confidence: 99%

Towards Autonomous Process Control—Digital Twin for HIV-Gag VLP Production in HEK293 Cells Using a Dynamic Metabolic Model

et al. 2022

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“…The substantial improvement of immune responses by increasing the antigen density on the surface of HIV-based virus-like particles (VLPs) as promising HIV-1 vaccines was recently reported . From a biochemical point of view, HIV-based VLPs are so-called enveloped VLPs and can be described as noninfectious nanoparticles with an average size ranging from 100 to 200 nm, which consist of a dense protein core formed by structural self-assembly of individual units from the HIV group-specific antigen (Gag) and a surrounding lipid bilayer originating from the host cell (Figure a). , Their surface is usually decorated with antigenic glycoproteins such as the transmembrane protein gp41 and the surface unit gp120, both of which can comprise synthetically shuffled epitopes from various HIV-1 strains representing the so-called mosaic antigens (Mos). , …”

Section: Introductionmentioning

confidence: 99%

“…Schematic sketch (a) of the bVLP (right) and of the eVLP (left) and (b) hypothesized structure of the bVLP (right) and of the eVLP (left) for the OSPM.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Electrokinetic Properties of HIV-Based Virus-Like Particles

Wolf,

Grau,

Rosengarten

et al. 2024

Langmuir

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The antigen density on the surface of HIV-based virus-like particles (VLPs) plays a crucial role in the improvement of HIV vaccine potency. HIV VLPs consist of a dense protein core, which is surrounded by a lipid bilayer and whose surface is usually decorated with antigenic glycoproteins. The successful downstream processing of these particles is challenging, and the high-resolution and cost-efficient purification of HIV-based VLPs has not yet been achieved. Chromatography, one of the major unit operations involved in HIV VLP purification strategies, is usually carried out by means of ion exchangers or ion-exchange membranes. Understanding the electrokinetic behavior of HIV-based VLPs may help to improve the adjustment and efficiency of the corresponding chromatographic processes. In this study, we investigated the electrokinetics and aggregation of both undecorated and decorated VLPs and interpreted the data from the perspective of the soft particle model developed by Ohshima (OSPM), which fails to fully predict the behavior of the studied VLPs. Post-Ohshima literature, and particularly the soft multilayer particle model developed by Langlet et al., provides an alternative theoretical framework to overcome the limits of the OSPM. We finally hypothesized that the electrophoretic mobility of HIV-based VLPs is controlled by an electrohydrodynamic interplay between envelope glycoproteins, lipid bilayer, and Gag envelope.

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“…Therapeutic vaccines could have an important role on functional cure and are being tested alone or in combination trials with immunomodulatory agents, broadly neutralizing antibodies (bNAbs) and/or latency reversing in the so-called “kick and kill” strategies [6,7]. The purpose of therapeutic vaccines is to modify host's immune response to HIV, either by redirecting it to the most conserved/vulnerable regions of the HIV viral proteome to mimic the response of spontaneous controllers [8 ▪ ,9] or by increasing its depth to cover more viral diversity [10].…”

Section: Introductionmentioning

confidence: 99%

Challenges of HIV therapeutic vaccines clinical trials design

Bailón

Alarcón-Soto

Benet

2022

Current Opinion in HIV and AIDS

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Purpose of the reviewTo discuss main challenges of therapeutic vaccine clinical trials design, implementation and analyses in the HIV cure field. Recent findingsTherapeutic vaccines are progressively being postulated as T-cell stimulating agents to use in combination HIV cure strategies, with the addition of immunomodulators, latency reversing agents and/or broadly neutralizing antibodies. Although promising strategies are rapidly evolving in preclinical studies using nonhuman primate models, translation into human testing in randomized controlled clinical trials is more challenging and expensive to conduct. Adaptive designs, access to cohorts of early-treated individuals, consensus on how to safely conduct analytical treatment interruptions, use of alternative statistical methods, development of point-of-care/home-based testing technologies and ensuring early engagement of communities where research is being developed are some of the critical aspects to consider to facilitate clinical trial development in the HIV cure field.

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Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes

Cited by 13 publications

References 66 publications

Towards Autonomous Process Control—Digital Twin for HIV-Gag VLP Production in HEK293 Cells Using a Dynamic Metabolic Model

Towards Autonomous Process Control—Digital Twin for HIV-Gag VLP Production in HEK293 Cells Using a Dynamic Metabolic Model

Investigation of the Electrokinetic Properties of HIV-Based Virus-Like Particles

Challenges of HIV therapeutic vaccines clinical trials design

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