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genengnews.com.
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Alternative Delivery Mechanisms
DNA vaccines lend themselves to several novel gene-delivery systems including nonpathogenic viral carriers. In July, GeoVax announced it had engaged the services of Vivalis, to adapt the French company’s EBx® cell lines to produce modified vaccinia Ankara (MVA), a smallpox virus component of GeoVax’ DNA HIV vaccine.
MVA is an attenuated virus created by passaging 500 times in chicken cells. The result is a virus that grows easily in chicken cells, but cannot replicate within mammalian cells. MVA is programmed with genes coding for HIV proteins, which are then expressed in the cytoplasms of infected cells. Like other DNA-based vaccines, GeoVax’s early-stage clinical product induces both antibody and T-cell immunity.
Previously, GeoVax expressed MVA in cultured, attachment-dependent chicken cells in small, multiple vessels. Vivalis’ avian stem cell-derived EBx lines produce suspension cultures, allowing the GeoVax MVA component to be grown and scaled to appropriate volumes in bioreactors.
In addition to carrying genes for expressing three of the major antigenic HIV proteins—GAG (an internal structural protein), POL (polymerase), and env (envelope)—MVA serves as a kind of adjuvant and immunizes against smallpox in the bargain. According to Harriet Robinson, Ph.D., svp of R&D at GeoVax, the vaccine can be used as a therapeutic as well as a preventive measure.
“Aside from protective immunity, the vaccine might also serve to control viral load in HIV without the need to take antiviral drugs. Administered early enough, it might even prevent immune system damage.”
The success of Merck’s Gardasil HPV can only be viewed as encouraging for developers of vaccines based on virus-like particles (VLPs). VLPs are recombinant structures that mimic the size and shape of a virus, but lack genetic material and, therefore, the ability to replicate. Their ability to present antigens in the same configuration as viruses is believed to be the source of the immune response VLPs induce.
In August, Novavax reported favorable results from a Phase I/IIa trial of its pandemic influenza VLP vaccine candidate. The unadjuvanted vaccine targets an Indonesian strain of avian flu with fatality rates above 80%. In this study, the vaccine induced dose-dependent levels of strong neutralizing antibodies.
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