Recent advances in the study of how the body's complex immune system works have helped scientists learn how to produce "tailor-made" vaccines that are both safer and can be targeted against organisms that resist vaccination.
A team from NUI Maynooth is at the forefront of this international research effort and has made important contributions to our understanding of how the immune system does its job.
"If we understand how the immune system works we can understand how to tailor the vaccines to target infections," explains Prof Kingston Mills, who heads the Infection and Immunity Group within Maynooth's Department of Biology.
This knowledge could also open up opportunities for new vaccines against organisms such as HIV and helicobacter pylori, the bacterium linked to stomach ulcers and cancer.
Vaccines have been around for 200 years but how they give immunity against infection has been something of a mystery until recent times, Prof Mills says. "Practically all the vaccines we have today were made without really understanding how the vaccine worked."
Detailed cellular and molecular studies of the main blood components that provide immunity have changed this however, and opened the way towards a new approach to the development of vaccines.
The immune system has both innate defences and "learned" or adaptive defences. The innate elements are non-specific and are triggered by any foreign invader and make use of phagoytic cells. The learned or "cell-mediated" components respond only to specific invaders such as measles or polio and depend on T-helper and T-killer cells.
Prof Mills's work focuses on the actions of T cells, in particular the T-helper cells. It was learned 10 years ago that there are two distinct types of T-helpers (Th). "My research has focused on understanding the role of these cells in immunity to infection and how their induction can be manipulated in new approaches to vaccine design and delivery."
The numbers of Th1 and Th2 cells are normally in balance but different organisms can stimulate one or the other preferentially. The quality of the immune response in part depends on which of these two are activated.
When a bacterium invades it carries a host of foreign substances that provoke the immune system. Some of these, known as antigens, are recognised by the immune system, which moves immediately to target and destroy them.
There are other toxins however, which have what is known as "adjuvant properties". These toxins are not recognised by the T cells but nonetheless cause a non-specific immune response.
The two T-helper cells respond differently to different adjuvants and Prof Mills is exploiting this selectivity in the search for new vaccines. "You can make designer vaccines on the basis of understanding how the adjuvant can stimulate the immune response," he says.
An example of T-helper response is seen in pertussis or whooping cough vaccine, he says. The original vaccine used a killed whole pertussis bacterium, which carried an adjuvant which stimulated Th1 cells.
The new vaccine uses only part of the bacterium and a different adjuvant that instead stimulates Th2 response. The net result is that while the new version is slightly less effective in protecting against pertussis, it is considerably safer to use.
The new genetic technologies have allowed researchers to take toxic bacterial adjuvants and modify their genetic code to make them non-toxic but still able to provoke an immune response.
"We are exploring what the bacteria are doing and using genetic engineering to knock out their toxicity," he said. "There is a drive to use the molecular technologies to exploit the benefits of the bacteria."
THE new designer vaccines will be based on taking a recognisable antigen from a bacterium and then combining it with an unrelated adjuvant which will cause a particular T-helper response, Prof Mills explained. "We are designing our vaccine delivery system having learned which response we want to get."
This may also provide new ways other than injection to deliver vaccines, he said. Bacterial adjuvants can produce a "very good immune response" in the form of a nasal spray.
His group is looking at new oral vaccines in conjunction with Elan and at nasal spray vaccines with Chiron.
An oral alternative to injected vaccines would be cheaper and safer to administer and so would have a tremendous impact on Third World vaccination programmes, he says.
The new vaccines hold great promise for the future, he says. In his recent Graves Lecture at the Royal College of Physicians of Ireland, Prof Mills predicted that within 10 to 15 years we should see new vaccinations for diseases such as meningitis, salmonella and H pylori and Third World diseases such as dengue, shigella, schistosomasis and malaria.