Scientists at the University of Michigan have developed a new vaccine formulation that fuses proteins derived from Listeria with viral components, and the combination of the two seems to generate a more potent immune response than conventional formulations based on live or weakened viruses, according to studies conducted in mice.
The vaccine is based on a bacterial protein called listeriolysin O (LLO), which is central to the process by which Listeria enters macrophage cells, one of the primary white blood cell types in the immune system.
Macrophages activate cytotoxic T-lymphocytes (CTLs) - another type of immune cell involved in immune protection against viral diseases. While CTLs are considered essential for an effective defence against viral diseases, they are often not adequately stimulated by conventional vaccine formulations.
By boosting the activity of CTLs along with the production of viral antibodies, the new vaccine formulation could provide a means of developing products that to date have either resisted the best efforts of vaccine developers or do not provide complete protection. One candidate would be HIV, but others include smallpox and influenza.
In preliminary studies using a mouse model of viral meningitis, a vaccine containing a recombinant version of the LLO protein was used to effectively immunise the animals against a lethal strain of lymphocytic choriomeningitis virus (LCMV) - with a 100 percent survival rate. In contrast, half of the mice died that were given a conventional meningitis vaccine formulation, while none of the non-immunized mice survived, they add.
Kyung-Dall Lee, an associate professor in the Department of Pharmaceutical Sciences at the University of Michigan, Ann Arbor, said the study represents the first time this experimental strategy has been shown to work in live animal models of viral infection.
US biotechnology company Advaxis has developed an intellectual property position in LLO-antigen fusion to form vaccine candidates, in partnership with GlaxoSmithKline Biologicals, and last year entered into a formal licensing agreement for the technology with a focus on cancer vaccines.
Their study appears in the debut (January) issue of Molecular Pharmaceutics.