7.1     In principle, any infectious disease may be combatted by vaccination, which stimulates the immune system to fight off infections which would otherwise take hold. This offers an alternative to treatment of established infections with antibiotics. Vaccination, which began in England in the late 1700s, has been one of the great medical successes of the 20th century, at least in those countries which can afford it; in the United Kingdom, for instance, vaccination has all but eliminated diphtheria, tetanus and measles, and reduced TB, mumps, Rubella (German measles) and whooping cough. The new "Hib" vaccine is highly effective against Haemophilus influenzae type B, formerly one of the chief causes of meningitis (Q 138). Most spectacularly, vaccination has eradicated smallpox worldwide[64], and has almost eradicated polio.

  7.2     Dr Geoffrey Schild and his colleagues from the National Institute for Biological Standards and Control (NIBSC), which works with the Department of Health, PHLS and the Centre for Applied Microbiology and Research (CAMR) to evaluate vaccines for the United Kingdom, told us of the prospects for further vaccines (p 316). Prospects over the long term are good: advances in gene sequencing, molecular biology and immunology, and the production of monoclonal antibodies, are opening up new possibilities.[65] SmithKline Beecham, who have around a quarter of the world market for vaccines, agree: there is at the moment "an explosion of activity in vaccine R&D" (p 482).

HIV

  7.3     Dr Schild said of HIV, "We know an enormous amount about the organism itself, but we still have no effective design for a vaccine. There are however a number of candidate vaccines under investigation" (Q 720). Dr Pillay of PHLS told us, "Progress has been very slow because we do not fully understand the nature of the immune response against HIV" (Q 590). SmithKline Beecham tell the same story, and do not expect success "in the immediate future" (p 483). The ABPI are collectively optimistic: "A vaccine for HIV infection is thought to be only a few years from marketing, assuming that remaining clinical trials are successful" (p 176).

Meningococcus

  7.4     Most meningococcal infection in the United Kingdom is due to Neisseria meningitidis bacteria of sero-group B (two-thirds of cases) or C (one-third). A vaccine against groups A and C, suitable for people exposed to infection but not for children under two, is already available; and more effective vaccines against group C may be in use by 2000. Group B, however, presents a greater scientific challenge, and an effective vaccine may be 5-10 years off or even more (Q 720).

TB

  7.5     The familiar BCG vaccine against TB, given to many British schoolchildren[66] and other people at high risk, "does not give very satisfactory protection against adult forms of the disease" (Q 721). Research is going on into alternatives, and the recent sequencing of the TB genome will "help considerably"; but a licence application may be 10-15 years away, particularly since clinical trials in TB take unusually long (Q 721), and because "the nature of protective immunity is not well understood" (SKB p 482).

Streptococcus pneumoniae (pneumococcus)

  7.6     Streptococcus pneumoniae causes pneumonia, meningitis and otitis media. Several vaccines are already available, but these are not suitable for children under two and are currently given only to older people at high risk; work is in hand on more effective ones. Vaccination could reduce the problem presented by penicillin-resistant pneumococcus (Klugman p 427), which is particularly menacing in poor countries where nothing more sophisticated than penicillin is affordable (Q 144). According to SmithKline Beecham (p 483), "Vaccines suitable for infants are now in advanced stages of development...it is expected that the new generation of vaccines will become available within the next five years".

Hospital infections

  7.7     There are no licensed vaccines against the common hospital infections, though some research is taking place.[67] Dr Corbel of NIBSC explained the difficulties: because of the large number of pathogens involved, most of which are found naturally in the body or the environment, universal comprehensive vaccination would be impossible. Pathogens must be targeted; he nominated Staphylococcus and Streptococcus. Patients must also be targeted; long-stay patients, and those awaiting elective surgery, might be vaccinated, but for acute patients vaccination would probably take effect too late (Q 731).

Barriers and bottlenecks

  7.8     According to Dr Schild, "The United Kingdom is in an excellent position to take an international lead in vaccine development" (Q 719). "We have a very comfortable way of working with industry, which does not create conflicts of interest..." (Q 727). However Dr Corbel drew attention to two areas where there may be room for improvement. First, where research is conducted in the public sector, producing enough vaccine of adequate quality for use in clinical trials can be difficult; "The private sector is probably better set up for it" (Q 727). Secondly, the system of regulation for clinical trials makes no distinction between large-scale commercial trials and small-scale academic trials; "There might be greater co-ordination between the regulatory agencies...to make the small-scale trial simpler than it is at the moment" (Q 728).

  7.9     SmithKline Beecham take a broader view (p 484): "The predicted breakthroughs in new vaccine development will not fulfil their promise if further public and political awareness of the health benefits and the cost-effectiveness of vaccination are not forthcoming. Present and future vaccines will need to be used more widely throughout the world to realise their full potential." Likewise the Royal Society (p 469): "Perhaps the question should now be asked whether the degree of risk that is deemed to be acceptable should be re-examined, and safety-testing regimes simplified in order to allow [vaccine] products to reach the market faster".

Surveillance for antigenic variation

  7.10     Vaccines do not encounter resistance in the same way as therapeutic agents; but they may run up against the phenomenon of antigenic variation. An antigen is a component of an organism which evokes an immune response. Some of these responses are protective against subsequent infections. In some organisms, antigenic variation produces a rapid succession of sub-types; for instance, influenza is so variable that a new vaccine is designed every few years. In others, e.g. the pneumococcus or the common cold, numerous sub-types co-exist, making design of a comprehensive vaccine difficult or impossible (Q 751). But the possibility also exists that an apparently effective vaccine may generate selective pressure in favour of precisely those antigenic variants which will break through it, and may even encourage variation which would not otherwise take place.

  7.11     Dr Schild told us that scientists are not yet sure whether this is happening or not. As we write, whooping cough is said to be breaking through vaccination in the Netherlands; but antigenic variation is not the only possible explanation (Q 740). He said, "We need increasing surveillance for the possibility of the emergence of variants that may grow through vaccine-induced immunity, because of the long lead time in vaccine development" (Q 741). Such surveillance is another task for the PHLS.

  7.12     International surveillance of influenza is already well established, under the aegis of the WHO; Dr Schild said, "The WHO influenza network is an example of international collaboration which time and time again has shown its value" (Q 748). Studies of protein structure may one day permit the design of an unbeatable 'flu vaccine; but for now, "We depend entirely on surveillance" (Q 752).

Research

  7.13     Vaccine research is well organised and resourced around the world, but the NIBSC tell us that much more needs to be done. "There are areas where serious deficiencies in basic scientific knowledge (e.g. in some aspects of immunology, microbial genetics, epidemiology and pathogenesis) are limiting the rate of progress in extending and improving the control of infectious disease by vaccination". Work is also needed on formulation and delivery of vaccines, to reduce the complexity and cost of vaccination programmes.

  7.14     United Kingdom vaccine research of a fundamental kind has received a significant boost with the establishment last year of the Edward Jenner Institute for Vaccines Research at Compton in Berkshire. The Institute will accommodate around 30 researchers, plus around 20 students and visiting scientists. Set-up costs have been found by Glaxo Wellcome, who will have first option on licensing of any products arising from research at the Institute; running costs will be shared between Glaxo Wellcome, the MRC, the BBSRC and the Department of Health.

  7.15     According to the NIBSC, the existence of antibiotics has skewed vaccine research away from diseases amenable to antimicrobial treatment. With the rise of resistance to antibiotics, priorities in vaccine research require to be re-assessed. In the long run, they suggest, prevention is better than cure: vaccination is more cost-effective over time than the continual race to develop new drugs faster than the bugs can adapt to resist them.

65   Surveyed in Chapter 4 of the POST report. Back

66   Current practice varies from district to district. Back

67   See for example SKB p 483. Back