Role of Virus-like Particles in Nanovaccines and Drug Nanocarriers

Viral-like Particles (VLPs)

Viral-like particles (VLPs) are nanoscale structures made up of assembled viral proteins that lack viral genetic material and are therefore non-infectious. VLPs are dispersed nanomaterials that can be produced in a variety of systems, including mammals, plants, insects, and bacteria. VLPs can be exploited as carriers for the delivery of bio- and nanomaterials, such as drugs, vaccines, quantum dots and imaging substances by virtue of the cavity within their structure. VLPs are gaining in popularity in the field of preventive medicine and to date, a wide range of VLP-based candidate vaccines have been developed for immunization against various infectious agents, the latest of which is the vaccine against SARS-CoV-2, the efficacy of which is being evaluated. In addition, structural proteins from viruses, such as human immunodeficiency virus (HIV), adeno-associated virus, Hepatitis B virus (HBV), Hepatitis C virus (HCV) and bacteriophages have been used to produce VLPs.

Fig. 1 Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers.

Advantages of VLP Vaccines

A largely exploited application of VLPs is their potential in vaccinology where they can offer several advantages over conventional vaccine approaches. Because of their size and shape, which resembles the actual size and shape of native viruses, these structures can efficiently elicit the immune responses and in VLPs lacking viral genomes there is no potential for replication within the target cells, which offers improved safety especially for immunocompromised or elderly vaccinees. While VLPs can stimulate both humoral and cellular immune responses they can also be loaded with immune-modulators, such as innate immune system stimuli to provoke more effective immune responses.

Production, Purification and Formulation of VLP Vaccine

The generic manufacturing process for a VLP-based vaccine generally consists of three main sections: (A) upstream processing (production), (B) downstream processing (purification), and (C) formulation. The first step in VLP production is to clone the viral structural genes of interest. Next, viral structural proteins with self-assembling ability are expressed in prokaryotic (bacteria, yeast) or eukaryotic (baculovirus/insect cell, mammalian cell and plant) expression systems. After harvesting and lysing the cells, to ensure removal of contaminating cell debris and aggregates a clarification step is performed. To obtain intact and more purified VLPs, further purification steps such as ion-exchange chromatography and ultracentrifugation are needed. A final purification step, polishing, is used to remove the residual host cell proteins and nucleic acids. In the last step of manufacturing process of VLPs vaccine development, sterile filtration and formulation is done to finally achieve a safe, efficient and effective product.

Fig. 2 Overview of VLP-based vaccine expression, purification and formulation.

VLP-based Vaccines against Emerging Infectious Diseases

To date 110 viral proteins from 35 viral families have been shown to be capable of assembly into the VLPs. Some of these VLP-based vaccines for human use have been approved for clinical use. Several other VLP-based vaccines are in various stages of design, production and approval.

HBV VLP-based vaccine

HBV, a virus in the family Hepadnaviridae, is the major causative agent of hepatitis B. HBV infection can lead to acute and chronic hepatitis and significantly increase complications and mortality. Epidemiological estimates suggest that two billion people in the world have serological characteristics of hepatitis B infection, 350 million of whom have chronic hepatitis B. Vaccination is currently the most effective way to prevent HBV, and VLP-based vaccines in use are made based on the self-assembly of HBV HBsAg into VLP particles.

HPV VLP-based vaccine

Persistent HPV infection is the major cause of the cervical cancer and genital warts. There are currently four HPV prophylactic vaccines on the market based on self-assembled VLPs that contain only L1 protein including Gardasil (Merck), Cervarix (GSK), Gardasil-9 (Merck), and Cecolin (Innovax). L1 protein is the major structural protein of the HPV that can be assembled into a VLP that is highly immunogenic and is able to elicit a type-specific immune response.

Human parvovirus VLP-based vaccine

Human parvovirus has two main structural proteins, VP1 and VP2. Human parvovirus B19 (HPVB19) VLPs composed of VP1 and VP2 proteins have reached clinical trials. These have been produced in the B/IC system in which sf9 cells are infected with two baculoviruses, leading to the production and self-assembly of immunogenic VLPs.

Norovirus VLP-based vaccine

Norovirus (NV) encodes a large protein that is broken into structural proteins VP1 and VP2 and regulatory NS1/2 to NS7 proteins. The NV VLP form of the NV VLP-based vaccine used in clinical trials is composed of the VP1 capsid protein that is expressed in the B/IC system (Sf-9) has been promisingly evaluated in clinical trials. VP1-based NV VLPs have also been produced using transgenic plants and these have also undergone early clinical trials.

Reference:

Nooraei, S. et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. Journal of nanobiotechnology, 2021, 19(1): 1-27.

* For research use only. Not intended for any clinical use.

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Role of Virus-like Particles in Nanovaccines and Drug Nanocarriers

Viral-like Particles (VLPs)

Advantages of VLP Vaccines

Production, Purification and Formulation of VLP Vaccine

VLP-based Vaccines against Emerging Infectious Diseases

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