CHAPTER 7 VACCINES |
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
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.
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).
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).
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).
7.5 The familiar BCG
vaccine against TB, given to many British schoolchildren
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
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".
7.7 There are no licensed
vaccines against the common hospital infections, though some research
is taking place.
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".
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
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.
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"
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.
For a survey of the whole subject, see Vaccines and their future
role in public health, Parliamentary Office of Science and
Technology (POST), July 1995. See in particular 3.2 and 5.2 on
the risks of side-effects and adverse reactions from vaccination,
which are of current concern but are not dealt with in our report. Back
Surveyed in Chapter 4 of the POST report. Back
Current practice varies from district to district. Back
See for example SKB p 483. Back