The current approaches are either treatment, notably with drugs, or prevention, primarily by vaccination, dependent upon the pathogen. The major unmet needs are in circumstances where neither acceptable therapeutic agents nor vaccination are available and the consequences or risks of infection are severe.

• Drug therapy is usually initiated once symptoms of infection have occurred, hence the patient is already suffering the consequences of infection. At this stage of infection, therapy does little to halt the onward transmission of the disease. Where drugs are available, they often lead to the development of resistant strains, as well as undesirable side effects. For viral infection, where the pathogen invades cells, eradication is usually impossible and at best, drugs only contain progression and hold viral replication in check.
• Prophylactic (preventative) vaccines are only available for a few pathogens. They utilise the immunological “memory” of a prior response to a particular antigen. The key is to achieve memory without first incurring the full infection, through various approaches. Though this clearly does not prevent subsequent contact with the pathogen, if this occurs, the body is able to mount a rapid cellular response to contain and rapidly eliminate the infection. However, strain variation and mutation can result in protection being inadequate.

Current vaccine technology seeks to modify the pathogen such that it is no longer disease-causing, while still inducing immunity. This is achieved by:

• Attenuation of the pathogen (altering the pathogen to render it harmless).
• Vaccination with killed pathogen (hence no risk from live pathogen).
• Subdivision of the pathogen (hence vaccinating with only a part of the pathogen).

However, each of these methods has major drawbacks: attenuated vaccines may revert to the harmful type (eg polio) or may be destroyed by an existing immune response before inducing immunity (eg BCG). Killed or subunit vaccines are unable to induce protective immune responses without the use of adjuvants and the safety risks of these non-specific immune stimulants pose severe limits to their utility. Development of DNA vaccines show promise, but as DNA is not normally taken up by dendritic cells, immune response levels can be low, even with the addition of adjuvants.

A number of high-profile outbreaks (eg TB, SARS, CJD, BSE and HIV), growing concern of potential future outbreaks (including pandemic influenza and bioterrorism) and recognition of the ability of pathogens to mutate (leading to drug resistance), highlights the scale of unmet needs. This has spurred interest in vaccines, as the return on the cost and duration of their development becomes evident. While many organisations’ programmes revolve around established approaches, often for lack of alternatives, it is clear that real improvements and returns must be based on new technology platforms, which appropriately address the unmet needs.

A number of initiatives have been launched, notably by the “G8 countries”, the WHO, the US Millennium Vaccine Initiative and through the Bill & Melinda Gates Foundation. Beyond supporting development, these build confidence that funds will be available for effective products, including for less developed countries.