Kissing the Epstein-Barr virus goodbye?
Box 2 | The future of vaccines
New techniques for the development and delivery of vaccines are aiding the search for effective immunisation strategies.
Gene guns and golden bullets
One such technique uses DNA to produce what are known as nucleic acid vaccines (sometimes called ‘naked DNA’ vaccines). Scientists isolate the genes from disease-causing bacteria or viruses that provide information to make specific antigens. These genes are then inserted into a plasmid (which is a genetic element capable of replicating independently of the chromosomal DNA) which, in turn, is injected into the patient. This can be done in the usual way with a hypodermic syringe into muscle tissue, or with a ‘gene gun’, which fires tiny gold particles coated with the DNA into the surface layers of the skin.
Once inside the body the plasmids penetrate host cells, where they start manufacturing antigens. These antigens, released over a long period, induce an active immune response by the body, including the production of both antibodies and specialised white blood cells (cytotoxic T lymphocytes).
The technique may be used to produce vaccines for both viral and bacterial infections; it shows such promise that clinical investigation of a possible AIDS vaccine has already begun.
‘Antigen factory’ vaccines
A similar technique involves the insertion of selected genes from a disease into benign bacteria or viruses. These are then administered to the patient and serve as a sort of antigen factory, using the inserted genes to churn out antigens of the disease-causing organism. These antigens invoke an immune response that will help protect the patient from a subsequent infection. Several ‘antigen factory’ organisms, including the cowpox virus, are being tested for use in HIV vaccines.
Making vaccines more effective
Conventional vaccines often use weakened or killed cells of the disease itself. While this has proved effective against many diseases, some vaccines developed by this technique produce occasional side-effects in patients. New methods using recombinant DNA technology have led to the development of many vaccines that use only a small part of the disease-causing organism or that use a harmless version of the microbe. For example, by removing genes from the cholera bacterium it becomes safe to use in a vaccine.
These methods produce extremely safe vaccines, but they are often less effective than whole-cell vaccines. A major area of vaccine research seeks ways of making such ‘subunit’ vaccines more effective in producing an immune response. This usually involves the use of what are called adjuvants, which are substances added to the vaccine to aid its operation. Conventional vaccines mostly use aluminium salt as an adjuvant, but recent work has tested oil-based emulsions that contain biodegradable material.
Vaccines have been developed at the University of Oxford in the UK that use genetically engineered viruses as a vector to carry genes for both antigen and adjuvant proteins. This technology could potentially help in the fight against diseases such as malaria and HIV that have been traditionally difficult to vaccinate against.
User-friendly vaccines
Vaccine development agencies recognise the importance of increasing the rate of childhood immunisation. One way of achieving this would be to develop vaccines that could be taken orally or nasally, rather than by injection.
With this in mind, researchers have investigated the use of what are called microcapsules. These consist of an inner reservoir of antigen surrounded by an outer, biodegradable polymer wall, through which the antigen is released slowly. Vaccines administered in this way have been shown to produce strong, sustained immune responses for some antigens. One advantage of microcapsules is that refrigeration is not required, making them suitable for remote regions.
Scientists are currently investigating the possible safety implications of having microcapsules in the body for extended periods. If the method proves to be safe, it may become widely used for vaccine administration.
Combining vaccines
Another way of boosting the rate of childhood immunisation would be to combine vaccines so that patients could be vaccinated against several diseases at one time. Some combinations are already available (the diptheria-tetanus-pertussis vaccine is one example), and researchers continue to seek ways of combining vaccines without reducing their effectiveness.
Linking chains
Armed with an understanding of the molecular structure of antigens for a particular disease, scientists are often able to replicate certain peptides of the antigen in the laboratory. These peptides show promise as vaccines because they can produce an immune response in patients. Indeed, the new Epstein-Barr virus vaccine currently under clinical trial is based on a peptide found on one of the virus’s antigens.
Nevertheless, despite considerable promise, there has been surprisingly little progress in the development of synthetic peptide vaccines. One reason for this might be that the peptides are too small and unstable to provoke an effective immune response.
Australian scientists at the Cooperative Research Centre for Vaccine Technology are pioneering work to polymerise (join together) small peptides. Early results suggest that the polymerisation process aids the potency of the peptides as antigens, and may also allow peptides against more than one disease to be included in the same molecular structure.
Vaccines don’t always target microbe-borne diseases
Trials in the USA have been conducted to test whether drug addiction can be treated with vaccines. Nicotine, cocaine and methamphetamine addiction could all potentially be treated this way. Vaccination for addiction gradually stimulates the immune system to produce antibodies that bind to the drug. This then progressively prevents the drug from entering the brain, reducing the effect on the body with minimal withdrawal symptoms.
The body’s own cancer cells may also be targeted by vaccines. By targeting the specific molecules that are found on the surface of tumour cells, vaccines can produce an immune response to cancerous cells. Cancer vaccines that show promise are those that target telomerase, an enzyme that makes cancer cells immortal.
Box
Box 1. Acquired immunity: Antibodies and T lymphocytes
Related site
New vaccines help kick drug habits (ScienceDaily, USA)
Page updated June 2008.