Virus-like particles (VLPs) resemble viruses, but are non-infectious because they do not contain any viral genetic material. VLPs can be produced in a variety of cell culture systems. VLPs are also a useful tool for the development of vaccines. Gene therapy efforts are focused on utilizing VLPs as a delivery system for genes or other therapeutics.
Perhaps one of the most exciting areas is the use of virus-like particles in vaccine development. This approach originated with the observation that sub-viral particles composed of a surface antigen were present in the blood of patients infected with hepatitis B virus and could be used as a vaccine (HbsAg). It was shown subsequently that eukaryotic expression systems, such as yeast and insect cells, could make HbsAg without the risk of contamination with other human viruses.
VLP preparations are all based on the observation that expression of the capsid proteins of many viruses leads to the spontaneous assembly of particles that are structurally similar to authentic virus. In practical terms, the fact that VLPs mimic the structure of virus particles usually means that the VLPs elicit strong humoral response.
The baculovirus expression system has been widely used for generation of VLPs due to the high productivity of the system and the ability to achieve rapid production scale implementation. VLPs have been successfully generated from many other Picornaviridae family members, including enterovirus, poliovirus and foot-and mouth disease virus (FMDV).
There remains some resistance to the VLP approach as a general vaccination strategy. In part this is due to some high profile disappointing results for VLP vaccines in early stages of developement, for example an ineffective early vaccine for HIV based on Ty VLPs. This example raises a point of caution for VLP vaccine designers ... as with any vaccine, VLPs rely on the long term host response to be effective.
...The development of an entirely new class of vaccines that target self-molecules involved in chronic diseases. Vaccines targeting CCR5 (for HIV infection), TNFalpha (for inflammatory disease), and IgE (allergy and asthma) have shown efficacy in animal disease models. ... Results demonstrate that a VLP-based vaccine can induce antibody responses against a self-antigen in humans.
VLP-based vaccines to prevent infection by two viruses, Hepatitis B Virus and Human Papillomavirus, have been approved for human use. Both of these vaccines safely and consistently induce high titer, durable antibody responses in humans.
During the past decade, VLPs have been mainly used as vaccines. In addition, there are a few reports where VLPs generated using nonstructural HIV proteins (e.g., Nef and Vpr) were used to deliver foreign proteins. Recently, Voelkel et al. reported that they were able to deliver proteins (GFP and functional Flp recombinase) to cells using murine retroviral particles.
The goal of protein-based therapies is restoration of biological functions by supplementing the absent or defective form of an essential protein. In this report, we describe an efficient and tractable protein delivery system using virus-like particles (VLPs). The VLPs we generated are derived from a modified version of the viral genome ... [making it] a safe and efficient system to deliver functional proteins into cells.
The engineered particles, called therapeutic interfering particles or TIPs, would persist for years in an individual patient and could be packed with genes that disrupt the functioning of HIV. ... In an HIV-infected individual, TIPs would transmit to others in the same ways as the natural virus - through unprotected sex or shared needles, for example. That means TIPs would, by design, penetrate high-risk populations that are responsible for a disproportionate share of the spread of disease and can be particularly difficult for public-health officials to reach.
Biochemist Leor Weinberger and colleagues at the University of California, San Diego and UCLA have proposed a fundamentally new intervention for the HIV/AIDS epidemic based on engineered, virus-like particles that could subdue HIV infection within individual patients and spread to high-risk populations that are difficult for public health workers to reach.