A NEW generation of vaccines that exploit natural 鈥渁larm bells鈥� in the immune system could be turned against killer diseases such as tuberculosis, malaria and HIV.
To press the panic button, the vaccines use adjuvants 鈥� substances that put the immune system on alert, making it more likely to notice the vaccine. Some vaccine injections are already augmented with adjuvant chemicals such as aluminium hydroxide, but the new vaccines have built-in genes for making their own adjuvants.
These adjuvants mobilise the immune system against the particular disease the vaccine targets, making the immune response more focused and potent when the body is infected by the real thing. Vaccines for malaria have already worked in mice, and human trials should start within two years.
Advertisement
The vaccines use harmless viruses that have been engineered to carry genes both for an antigen 鈥� a protein from the virus or organism that causes the disease that is being targeted 鈥� and for an adjuvant protein.
The virus is seized by antigen-presenting cells (APCs), which are sentinels that patrol the body and apprehend potential attackers before breaking them down and presenting their components to lymphocytes 鈥� the white blood cells that are primed by a vaccine to defend the body against the real disease. Once inside an APC, the virus tricks the cell into manufacturing tiny amounts both of the antigen protein and of the adjuvant protein.
Importantly, the adjuvant proteins used by the vaccines press alarm buttons within the cell called RIG-like receptors. This fools the cell into thinking that it has captured a harmful virus, making it more sensitised than usual and therefore more likely to mobilise the rest of the immune system to fight the accompanying antigen protein (see Diagram). This helps train the immune system to fight infection by the disease that carries the antigen in question. 鈥淚t is the first intracellular adjuvant,鈥� says Adrian Hill, head of the team at the University of Oxford that is developing the vaccines.
鈥淭he cell is fooled into thinking that it has captured a harmful virus, making it more sensitised than usual鈥�
Last week, Hill鈥檚 team joined forces with British company Cambridge Biostability in a plan to develop such vaccines against the 鈥渂ig three鈥� diseases 鈥� malaria, TB and HIV 鈥� and to make them storable without refrigeration in poor countries, where they are most needed. The company seals vaccine particles inside tiny sugar spheres that prevent their contents from decaying either over time or in hot climates. The spheres can be stored indefinitely in injectable liquids. Once injected into the bloodstream, the sugars and the liquid break down, releasing the vaccine (New 杏吧原创, 23 October 2004, p 9). 鈥淚f these vaccines are going to be given, they must be deployable in the developing world and cheap,鈥� says Hill.
Bruce Roser, chief scientific adviser of Cambridge Biostability, is confident that Hill鈥檚 vaccines can be stored 鈥渓ive鈥� within the spheres, as the company has already achieved this with a virus-based measles vaccine.
Marie-Paule Kieny, director of vaccine research at the World Health Organization in Geneva, says that the approach is radical for vaccinology. Genes have been tried as a way to stoke up immunity in cancer therapies, but the idea of equipping vaccines with genes that specifically trigger 鈥渁larm鈥� receptors is new. 鈥淚t is quite complicated,鈥� says Kieny, and it may be difficult to fine-tune the vaccine so the immune system doesn鈥檛 over or under-react to the signals. Using the approach to combat the 鈥渂ig three鈥� is 鈥渙ptimistic, to say the least鈥�, she says.
