Virus-like Particles

Using an approach that had proved successful with many other viruses, including rotaviruses and parvoviruses, scientists were able to use a cell expression system to create a copy of the virus’ lipid capsule, but with no genome inside. This lipid vesicle expressed the same surface glycoproteins (GPs), such as VP 40, thus making it highly immunogenic. Without its genome, however, this VLP was unable to replicate, thus rendering it harmless to all cells. This was an important breakthrough for two reasons. Not only could it be used as a possible vaccine approach, but it would allow study of Ebola’s structure outside of level 4 labs, which are expensive and cumbersome to build and maintain. (Ebola virus shown on the left; Ebola virus-like particles shown on the right. Click image for larger version.)

Using a the human embryonic cell line 293T, which was cotransfected with a plasmid vector encoding for Ebola VP 40 and GPs, researchers were able to produce copies of the virus sheath. The resulting product was purified through gradient techniques, electron microscopy and western blotting to obtain a purified sample of VLPs.

These VLPs were shown to be morphologically identical to the real Ebola virus. To asses their immunogenicity, mice were vaccinated with the VLPs, and then challenged to see if there was any cellular response. Upon investigation of primary and secondary lymphoid organs, it was found that mice injected with the VLPs had statistically significant changes in their B and T cell levels when compared to the control group. There was also an associated release of cytokines, further confirming the immune response in these mice. Murine (mouse) dendritic cells were also challenged with the VLPs in vitro, in order to test whether the DCs would undergo functional and phenotypic changes, including increased expression of MHC and costimulatory molecules. Evidence of both of these changes was found. This discovery is of special note, as it is the DC cells that play a crucial role in any adaptive response. Additionally, it was also shown that the VLPs induced a high titer of IgG (see antibody section).

Thus we can see that VLPs offer an attractive vaccine option for several reasons. With no genome, the VLPs are unable to infect a host, but at the same time elicit a response from both the innate and cell mediated arms of the immune system. Although the specific mechanisms that the immune system responds with are still being explored, it is probable that antibodies in concert with CD4+ and CD8+ T cells are central in the immune response. As of this writing, research continues in the effort to create a successful vaccine using this approach. The next step will probably involve a primate model, and if this proves successful, a human trial will probably soon be in the planning.

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This page last updated: 14 April 2004.