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Virus-like Particles: Tools for your infectious disease research

Virus-like particles (VLPs) are non-infectious nanoparticles that assemble from recombinantly expressed viral proteins but lack the viral genome required for replication and infection. Because they are non-infectious VLPs do not require the same level of biosafety containment as competent native viruses but retain the self-assembling and antigen-presenting capabilities that can be manipulated for innovative therapeutics uses. It is encouraging that a number of VLP-based vaccines are licensed for human use including Engerix® and Recombivax HB® hepatitis B vaccines as well as Cervarix® and Gardasil® human papillomavirus-like particle-based vaccines for the prevention of cervical cancer. Many others are in development to treat current viral threats like Zika virus, BK Virus, and JC Virus. VLPs may offer the means to bypass the long-standing obstacle to targeted drug delivery that may minimize side effects and enhance efficacy and offer effective treatments against many pathogens[1].

VLP types3

Image borrowed from Naskalska et al. Pol J Microbiol. 2015;64(1):3-13.

Types of  VLPs

VLPs can come in all shapes and sizes. One major distinction is that VLPs can be non-enveloped or enveloped. Non-enveloped VLPs will bud from the host cell and not carry the host cell membrane. The outer structure of the VLP is formed from assembly of the recombinant viral proteins. Enveloped VLPs will express some of the viral proteins in the host cell membrane. They will also express a viral protein that will support assembly and budding of the viral proteins from the host cell. When these VLPs bud, they carry the host cell membrane containing the viral proteins on the surface of the VLP.

Expression Systems for generation of VLPs

VLPs can be produced in various expression systems that can be scaled for bulk production. Currently approved VLP-based vaccines have been produced in yeast, insect, Escherichia coli, plant, and mammalian cells. Bacterial expression systems are quick and cost-effective, but such systems lack post-translational modification ability (such as glycosylation) that may be required for an effective host immune response. Mammalian expression systems are more suitable for post-translational modifications, however, manufacturability can be problematic. Yeast and insect cell-based expression of VLPs combine the robust manufacturability of the bacterial system and post-translational modification capability of the mammalian system.

Use of VLPs in vaccine research- Case Use

IBT Inc has extensive experience in the expression of the filovirus VLPs composed of a matrix viral protein (VP40). This is sufficient to drive budding of the VLPs and mimics the distinct filamentous structure of the authentic virus. In addition of viral glycoprotein (GP), the major determinant of protection against filovirus infections, to the VLPs enables it to elicit protective immunity. Our VLPs also included the viral nucleoprotein (NP), which localizes in the core beneath VP40 and is hypothesized to provide additional protective T-cell epitopes. We achieve this using a combined mammalian (HEK293T) and insect (SF9) cell-based expression platform. The resulting VLPs have demonstrated protection in nonhuman primates against three different species of ebolaviruses including homologous protection using Ebola virus (EBOV) and Sudan virus (SUDV) VLPs[2], as well as heterologous protection against Tai Forest Virus (TAFV) by EBOV VLP[3]. This is relevant as aerosolized filoviruses are considered to be potential biothreat agents.

See links below to see related publications on this topic:
[1] Advances in Virus-Like Particle Vaccines for Filoviruses. Kelly L. Warfield and M. Javad Aman, J Infect Dis. 2011 Nov 1; 204(Suppl 3): S1053–S1059. doi: 10.1093/infdis/jir346.

[2] Ebola Virus-Like Particle–Based Vaccine Protects Nonhuman Primates against Lethal Ebola Virus Challenge. Kelly L. Warfield, et al, J Infect Dis. 2007 Nov 15;196 Suppl 2:S430-7.

[3] Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles. Kelly L. Warfield, et al, PLoS One. 2015 Mar 20;10(3):e011888.

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Fig. 1 Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain). Inoculum 1xLD90=1.0E+05 PFU/mouse
Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain) 1.0E+05 PFU/mouse
Survival and weight change in BALB/c mice challenged with INFV A/ Texas/36/91 (H1N1) and treated with antiviral Osletamivir Phosphate (Tamiflu)
Lung viral load and Survival (30 % weight loss cut-off) in BALB/c mice challenged with INFV H3N2 A/HK/1/68.