Vaccines an overview and update vaccine jab

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                                                                                                                                                                                             Continuing professional development
Vaccines: an overview and update
According to the World Health Organization, the two public health interventions that have had the greatest impact on the world’s
health are the supply of clean water and vaccines. More recently, interest has surrounded the development of a vaccine for avian
influenza. In this article, Yvonne Perrie outlines current vaccination schedules and advice

     accines prevent death on a large scale, but

V    only if enough people are immunised. If
     most of the people within a population
are vaccinated against an infection, those who
are not will still be protected because spread
of the pathogen is blocked. This is known as
“herd immunity”. However, this immunity
relies on public support of vaccination pro-
grammes which, in turn, strongly depends on
perception of risk versus benefit. For exam-
ple, the controversy relating to the safety of
the combined measles, mumps and rubella
(MMR) vaccine stemming from proposed
links with autism has had a detrimental im-
pact on the protection of children from these
diseases within the UK. While most of the
researchers who initially proposed this link                                                                                     Identify knowledge gaps
                                                                                        Mike Wyndham Medical Picture Library

subsequently retracted their speculations, the                                                                                   1. How do vaccines work?
damage in terms of public confidence was                                                                                         2. What different types of vaccine are available?
done. A marked reduction in the percentage                                                                                       3. What is the current childhood vaccination
of the population immunised against MMR                                                                                             programme?
(from 92 to 82 per cent) occurred across the
UK, with some areas of London reporting an                                                                                       Before reading on, think about how this article may
uptake 20 per cent lower than the national                                                                                       help you to do your job better. The Royal
average.1 The World Health Organization rec-                                                                                     Pharmaceutical Society’s areas of competence for
ommends an immunity level of 95 per cent to        The population                                                                pharmacists are listed in “Plan and record”,
prevent disease outbreaks. The reduction in        immunised against MMR                                                         (available at: This
MMR vaccinations has been reflected by             has fallen from 92 to 82                                                      article relates to “health promotion”.
increased reports of measles and mumps in          per cent in the UK
the UK and, in response, some health author-
ities are holding publicity events and training                                                                                for specific immunity to be generated.
primary care staff to encourage uptake of the                                                                                  Generally, the closer the vaccine is to the orig-
combined vaccine.                                                                                                              inal infectious agent the better its efficacy. Live
                                                                                                                               attenuated systems tend to be more effective
Basic principles of vaccination                                                                                                than inactivated ones or cellular extracts (see
Vaccination is based on two key elements of                                                                                    below for further discussion of vaccine types).
adaptive (acquired) immunity: specificity and                                                                                  However, the enhanced efficacy of live vaccines
memory.When an infection occurs, the body                                                                                      is accompanied by increased adverse effects.
produces cells capable of fighting it and
memory cells specific to the pathogen are                                                                                      Risks and benefits of vaccines
generated. Memory cells implement a faster                                                                                     What is deemed an acceptable risk of adverse
and stronger response on a second encounter                                                                                    effects should be considered in relation to the
with an infectious agent compared with the                                                                                     risks associated with a disease. Panel 1 (p209)
response on first exposure to the pathogen.                                                                                    gives examples of the risks of vaccinations
    Vaccines allow an individual to acquire                                                                                    compared with their corresponding disease.
specific immunity to an infectious agent                                                                                           It could be argued that some anti-vaccine
without having to suffer an initial infection.            Yvonne Perrie, PhD,                                                  sentiment stems from the success of immuni-
This is important because the primary                     MRPharmS, is a senior                                                sation programmes. Developed countries no
response to a natural infection is often too              lecturer in pharmaceutics                                            longer have major incidences of many diseases
slow to prevent serious symptoms develop-                 at the school of life and                                            so people are more likely to question the need
ing.                                                      health sciences, Aston                                               for vaccination. In developing countries, the
    The aim of vaccine development is to                  University, Birmingham,                                              risk versus benefit ratio can be different. For
modify a pathogen (or its toxins) so that it is           and a board-director of the                                          example, in developed countries, access to
harmless without loss of antigenicity. This is            Academy of                                                           effective health care significantly limits mor-
possible because antibodies and memory cells              Pharmaceutical Sciences.                                             tality rates to rotavirus but in countries where
within the immune system recognise particu-               The APS is dedicated to the                                          access to doctors and standard fluid rehydra-
lar areas of antigens, known as epitopes, rather          promotion of                                                         tion treatments are limited these rates soar and
than the whole organism or toxin. As long as              pharmaceutical sciences.                                             vaccination is more important. In 1998,Wyeth
the body is presented with such epitopes it               Information can be found                                             Pharmaceuticals introduced a rotavirus vac-
does not need to encounter the full pathogen              at                                                     cine but, less than a year later, this was with-                                                                                                                                18 February 2006 The Pharmaceutical Journal (Vol 276) 209
                                                                                                                   ated vaccines, inactivated vaccines offer ad-
                    Panel 1: Comparison of risks of disease and vaccine                                            vantages in terms of reduced adverse effects.
                                                                                                                   For example, there is no risk of induction of
                    Disease Risks from natural infection          Potential adverse effects of vaccination         disease via reversion or mutation to an infec-
                                                                                                                   tious agent, as is the possibility with live at-
                    Measles Rash and fever (almost all)           Fever (one in six)                               tenuated systems. In 2004, within UK
                    (MMR) Ear infection (1 in 20)                 Temporary pain and stiffness of joints           vaccination programmes the live polio vac-
                            Fits (one in 200)                       (most teenage or adult women)                  cine was replaced with an inactivated one (see
                            Inflammation of the brain (one        Mild rash (one in 20)                            Panel 3).
                               in 1,000; three out of 20 will     Seizures (one in 3,000)                              In 2005, a new cholera vaccine (Dukoral)
                               die from this and 20–40 per        Swelling of glands in cheeks or neck (rare)      was launched in the UK. It contains killed
                               cent are left with permanent       Temporary low platelet count (one in             whole Vibrio cholerae 01 bacteria.The vaccine
                               after-effects)                       30,000)                                        triggers a local intestinal protective immune
                            Low platelet counts (one in           Severe allergic reactions (less than one in      response, which prevents bacterium from
                               3,000)                               1,000,000), including deafness,                attaching to the intestinal wall, blocking
                            Subacute sclerosing                     seizures coma and inflammation of the          colonisation. Dukoral is an oral suspension
                               panencephalitis (one in              brain (rates similar to unvaccinated           and is added to a mixture of sodium hydro-
                               8,000), which results in             children)                                      gen carbonate buffer dissolved in water.
                               progressive spasticity,
                               dementia and death                                                                  Cellular extracts or toxoids Vaccines
                            Death (one in 2,500–5,000)                                                             based on cellular extracts (highly purified
                                                                                                                   proteins, synthetic peptides, parts of cells, sur-
                    Hib         Hib meningitis (three in five)    Soreness, swelling and redness at injection      face antigens) or toxoids (exotoxins detoxi-
                                Long-term effects include fits,       site (about 10 per cent)                     fied, for example, by using formalin) cause
                                  intellectual impairment,        Fever (one in 20)                                fewer adverse effects than live attenuated and
                                  vision and hearing loss,        Transient fever, headache, tiredness,            inactivated vaccines. Genetic engineering
                                  movement problems                   muscle ache                                  facilitated the construction and production of
                                  behaviour alterations (one to   Irritability, inconsolable high-pitched crying   antigens that can be used. For example, the
                                  three in 10)                    Fits (rare)                                      hepatitis B vaccine is cloned in yeast and
                                Septicaemia (one in 10)                                                            manufactured using biotechnology rather
                                Death (one in 20)                                                                  than, as previously, being purified from the
                                                                                                                   blood of hepatitis B carriers. This has
                                                                                                                   enhanced production and safety of the vac-
                 drawn as a result of the associated risk of in-                                                   cine and has reduced costs.
                 tussusception which appeared in one in                                                                The disadvantage is that vaccines based on
                 12,000 children vaccinated. New rotavirus                                                         cellular extracts or toxoids are often poorly
                 vaccines are now in clinical trials.                                                              immunogenic and require adjuvants (sub-
                                                                                                                   stances that non-specifically enhance the im-
                 Types of vaccine                                                                                  mune response to an antigen.) Currently
                 The type of antigen used in a vaccine depends                                                     licensed adjuvants include aluminum hydrox-
                 on many factors and influences their efficacy.                                                    ide or phosphate (used in diphtheria, tetanus
                 There are three main types of antigenic prepa-                                                    and hepatitus B vaccines) and AS04 (this con-
                 rations currently available: live attenuated vac-                                                 tains aluminium and the bacterial lipid,
                 cines, inactivated vaccines and vaccines                                                          monophosporyl lipid A). Toxoids, in addition
                 containing cellular extracts or toxoids.                                                          to being successful vaccines in their own
                                                                                                                   right (eg, tetanus), are used to increase the
                 Live attenuated vaccines Attenuation                                                              immunogenicity of vaccines, such as
                 (weakening) of live infectious agents is used to                                                  Haemophilus influenzae type b (Hib), which
                 eliminate or reduce the virulence of the agent                                                    contains a polysaccharide unit from the bac-
                 while aiming to retain its antigenicity.This can                                                  terium conjugated to diphtheria or tetanus
                 be achieved by various means, including treat-                                                    toxoids. New adjuvant systems being tested
                 ment with heat, chemicals or enzymes, or ge-                                                      include particulate delivery systems, such as
                 netic modification. For example, the Bacillus                                                     liposomes, niosomes, virus-based particles and
                 Calmette-Guérin (BCG) vaccine contains a                                                          microspheres.
                 live attenuated mutant of Mycobacterium bovis
                 isolated from serial subcultures. The primary                                                     Vaccination programmes
                 mechanism of weakening the bacillus is to                                                         The goal of any vaccination is the induction
                 remove the secreted lytic function that it                                                        of an appropriate and effective immune
                 needs to invade lung interstitial tissue.                                                         response, but precisely what constitutes an
                     Live vaccines should not be given to peo-                                                     effective immune response for many diseases
                 ple with impaired immune response. For                                                            is still unclear. Efficacy is known to depend
                 example, vaccinations with such products                                                          on a range of factors including age and
                 should be postposted to until at least three                                                      immune status.Vaccine efficacies can range
                 months after stopping corticosteroids or other                                                    from 70 to 98 per cent effective (ie, vaccina-
                 immunosuppressants.                                                                               tion does not guarantee immunity and not all
                                                                                                                   the recipients will produce appropriate anti-
                 Inactivated vaccines Inactivated vaccines                                                         body levels for protection against infection).
                 contain whole bacteria or viruses that have                                                           The presence of antibodies are often con-
                 been killed, usually by heat or chemicals.                                                        sidered as markers of protection. Specific lev-
                 While generally less effective than live attenu-                                                  els of antibodies are considered protective

210   The Pharmaceutical Journal (Vol 276) 18 February 2006                                                                       
                                                                                                                                                                          Continuing professional development
against infections such as hepatitis                                                                          queries about vaccinations as an opportunity
(>10mIU/ml), diphtheria (>100mIU/ml)                                                                          to give advice on preventing malaria and diar-
and tetanus (>100mIU/ml) but for many                                                                         rhoea.
others, correlations of efficacy are less obvious                                       Ensuring                  Travellers should be advised to organise
and require further investigations.3                                                                          vaccinations well in advance of travel.Time is
   The length of protection conferred by a                                              effective             needed for courses of vaccinations to be com-
vaccine varies. For example, immunity given
by hepatitis A vaccine has been estimated at
                                                                                    participation in          pleted (if a primary course of vaccines is re-
                                                                                                              quired this can take up to three months),
between 10 and 20 years for different brands.                                       current vaccine           antibodies to be produced and any adverse re-
Information can be found in the summary of                                                                    action to be dealt with. For example, it can
product characteristics. One study of hepatitis                                       programmes              take up to four weeks for full immunity to de-
B vaccine suggested that giving a full primary                                                                velop following vaccination against Japanese
course of the vaccine to a healthy person                                              will have a            encephalitis.
results in lifelong immunity. However, many
health care workers are advised to have boost-
                                                                                       significant                In addition, there are recommended inter-
                                                                                                              vals between doses and between different vac-
ers every five years.                                                                impact on the            cines. It is recommended that live vaccines
   The vaccines most commonly encoun-                                                                         should be given at least three weeks apart, but
tered by pharmacists are those for children or                                          control of            the rationale behind this comes from observa-
travellers. Panel 2 lists these. Panel 3 (p212)
describes recent changes to the childhood
                                                                                         disease              tions that the take rates of smallpox vaccines
                                                                                                              were reduced if another live vaccine had been
vaccination programme.                                                                                        given shortly before. According to the
                                                                                                              Department of Health, there is no data to sup-
Travellers The vaccinations travellers                                                                        port this with current vaccines and, in prac-
require will depend on the country to be vis-                                                                 tice, many vaccines are given simultaneously.
ited and the type of trip (eg, business travel or                                                             Most inactivated vaccines can be given at the
a package holiday may not present the same                                                                    same time as other vaccines (different admin-
risks as long-term travel in rural areas) and                                                                 istration sites are used) but concurrent admin-
individual circumstances need to be assessed.                                                                 istration can make it difficult to determine
Travellers should be referred to their GP or a                                                                what has caused an adverse reaction. Most
vaccination centre, but pharmacists could use                                                                 courses of travel vaccines can be administered
                                                                                                              over four weeks. Some countries may require
                                                                                                              travellers to have certificates of vaccination.
   Panel 2: Current immunisation schedules
                                                                                                              Tetanus Patients who have a wound may ask
   Immunisation groups                     Vaccine                                                            if a “tetanus jab” is needed. This depends on
                                                                                                              whether or not the patient is fully immunised
   2, 3 and 4 months old*                  Diphtheria, tetanus, pertussis, polio and Haemophilus              (five doses of tetanus vaccine is thought to
                                             influenzae B (as a single injection; DTap/IPV/Hib)               confer life-long immunity for people who do
                                                                                                              not travel outside the UK) and on the wound
                                           Meningococcal group C injection                                    type. In the UK, children are given three doses
                                                                                                              of the tetanus vaccine as part of a combined
   12–15 months old*                       MMR injection                                                      vaccine (see Panel 2).This confers primary im-
                                                                                                              munity and two booster doses are recom-
   3–5 years (pre-school)                  Diphtheria, tetanus, pertussis and polio (as a single injection)   mended (the first given before starting school
                                                                                                              and the second before leaving school). Patients
                                           MMR injection                                                      who are not fully immunised (eg, incomplete
                                                                                                              primary immunisation or missed boosters)
   13 to 18 years                          Adsorbed diphtheria (low dose), tetanus and polio (as a single     may require a reinforcing dose. Patients with
                                             injection)                                                       tetanus-prone wounds (eg, puncture wounds,
                                                                                                              particularly those contaminated with soil) are
   Women of child-bearing     MMR injection                                                                   likely to require a dose of tetanus im-
   age susceptible to rubella                                                                                 munoglobulin (to confer immediate protec-
                                                                                                              tion) and a course of antibiotics.
   Adult (if not previously                Diphtheria (low dose), tetanus and polio (as a single                  Travellers are advised to have booster doses
   immunised)                                injection; three doses at intervals of four weeks)               of tetanus every 10 years.

   High-risk groups                        BCG, hepatitis A, hepatitis B, influenza, pneumococcal,            Future vaccines
   (eg, health care workers)                 tetanus                                                          Two new vaccines against the sexually trans-
                                                                                                              mitted human papillomavirus (HPV) are now
   Travellers                              Cholera, diphtheria, hepatitis A, hepatitis B, Japanese            approaching market. Some strains of human
                                             encephalitis, meningococcal meningitis, polio, rabies,           papillomavirus (eg, HPV 16 and 18) cause cer-
                                             tetanus, tick-borne encephalitis, tuberculosis, typhoid,         vical cancer while others (eg, HPV 6 and 11)
                                             yellow fever                                                     can cause genital warts. Currently, clinical trial
                                                                                                              data for both vaccines look promising with
* A new routine vaccination schedule (to take effect later this year or in 2007) is as follows:               each preventing persistent infection in 100 per
2 months old      DTap/IPV/Hib + pneumococcal vaccine                                                         cent of vaccinated women and reducing cer-
3 months old      DTap/IPV/Hib + meningoccal group C vaccine                                                  vical abnormalities by more than 90 per cent.4
4 months old      DTap/IPV/Hib + pneumococcal vaccine +meningoccal group C vaccine                            The vaccines, made by Merck & Co (Gardasil)
12 months old Hib booster + meningoccal group C booster                                                       and GlaxoSmithKline (Cervarox), contain a
13 months old MMR + pneumococcal booster                                                                      viral protein called L1, which forms the bulk                                                                                                             18 February 2006 The Pharmaceutical Journal (Vol 276) 211
                                                                                                                       There remains an urgent need for new
                    Panel 3: Recent changes to the UK childhood                                                    vaccines, with protection against human
                                                                                                                   immunodeficiency virus and malaria being
                    vaccination programme                                                                          high on the wish-list. A better vaccine against
                                                                                                                   TB in adults is also desirable — although the
                    2006 — Changes to the childhood immunisation programme Following the                           current BCG vaccine protects young children
                    introduction of pneumococcal vaccination in the US (where pneumococcal infection in            against miliary TB, it is thought to be ineffec-
                    young children, caused by strains on which the vaccine is based, fell by 94 per cent) the      tive in preventing pulmonary TB in adults.
                    Department of Health has announced that children in England and Wales will routinely be        New cancer vaccine therapies, which may act
                    vaccinated against pneumococcal infection in order to prevent meningitis, septicaemia and      by a variety of underlying mechanisms, are
                    pneumonia (PJ, 11 February, p160). The vaccine, Prevenar, is licensed for use in infants.      continuing to inch forward. In the meantime,
                        In addition, the current three doses of meningococcal group C will be rescheduled (to      ensuring effective participation in current vac-
                    be given at three and four months of age, with a booster at 12 months to maximise              cine programmes will have a significant impact
                    protection in the first two years of life) and a booster dose of Hib is to be given at 12      on the control of disease and thus remains an
                    months (to extend protection against haemophilus influenzae B).                                objective for all health care professionals.
                        The changes to the childhood immunisation schedule will come into effect later this
                    year or in 2007 (see Panel 2).
                    2005 — Withdrawal of BCG vaccination Following a review by the Joint Committee on              1. Fitzpatrick M. MMR: risk, choice, chance. British Medical
                    Vaccination and Immunisation, immunisation of children with BCG through the national              Bulletin 2004;69:143–53.
                    schools’ based programme was withdrawn and only at risk groups (including infants living       2. Dukoral, a new cholera vaccine, licensed in the UK.
                                                                                                                      Pharmaceutical Journal 2004;272:663.
                    in areas where the incidence of tuberculosis is greater than 40 in 10,000, infants whose
                                                                                                                   3. Bramwell VW, Perrie Y. The rational design of vaccines. Drug
                    parents or grandparents were born in a country with this incidence of TB and previously           Discovery Today 2005;10:1527–34.
                    unvaccinated new immigrants from high prevalence countries for TB) are recommended to          4. Cohen J. High hopes and dilemmas for a cervical cancer
                    receive the vaccine. This brings the UK in line with the WHO perspective, which                   vaccine. Science 2005;308:618–21.
                    recommends a single dose of BCG should be given as soon as possible after birth in all
                    populations at high risk as a means of minimising the harmful effects of TB infection in the   Resources
                    first year of life.                                                                            ■ is a good site to recommend to
                                                                                                                       patients for basic information on vaccines.
                    2004 — Switch from live to inactivated polio vaccine An inactivated polio vaccine              ■ The National Travel Health Network and Centre
                    (an injection) replaced the live vaccine (oral) because the risk of contracting polio is so provides health information for travellers.
                    low that the benefits associated with using the more effective live vaccine are outweighed     ■ Department of Health. Immunisation against infectious
                                                                                                                     disease 1996 — “the green book”. Available at
                    by the rare adverse events associated with the vaccine itself. These risks, while low (1 in
                                                                                                            (accessed 13 February 2006).
                    1.5 million doses), include the capacity to generate infectious polio virus through mutation   ■ Department of Health.Health information for overseas travel
                    and live vaccine associated paralysis.                                                           — “the yellow book”. Available at
                                                                                                                     (accessed 13 February 2006).
                    2004 — Use of cellular extract pertussis instead of whole-cell pertussis vaccine A             ■ A CPD article to be published in September will cover
                    new vaccine containing acellular pertussis (Pediacel) was shown to offer protection              influenza, including influenza vaccines.
                    against clinically typical pertussis equal or better than the whole-cell vaccine. The switch
                    should reduce the risk of adverse events because reactions to the vaccine are less
                    frequent than when whole-cell vaccines are used.                                                  Action: practice points
                                                                                                                      Reading is only one way to undertake CPD and the
                    2004 — Introduction of a “five-in-one vaccine” A vaccine incorporating diphtheria,                Society will expect to see various approaches in a
                    tetanus, pertussis (acellular), polio (inactivated ) and Hib was introduced to reduce the         pharmacist’s CPD portfolio.
                    number of injections required.                                                                    1. Write bullet points for how you would respond
                                                                                                                         to a parent worried about the combined MMR
                    2004 — Thiomersal not used in new vaccines Thiomersal (ethylmercury) is a                            vaccine; aims to
                    mercury-based preservative that is used in vaccines such as the diphtheria, tetanus and              provide parents and guardians with clear
                    whole cell-pertussis. Although there is no evidence that relates thiomersal to adverse               information on MMR.
                    events (including a recently proposed link to autism), as part of a global strategy within        2. Evaluate how you are supporting the uptake
                    Europe and the US there is a move to reduce avoidable exposure to mercury and it was                 and implementation of vaccine programmes
                    recommended that vaccine manufacturers phase out its use wherever possible.                          in your area and identify how you can extend
                                                                                                                         your role in offering advice on the various
                                                                                                                         vaccines available for children and travellers.
                 of HPV’s outer shell. Both vaccines use L1                                                           3. Consider the potential benefits of the new
                 from the HPV 16 and 18 genotype. Gardasil,                                                              cervical cancer vaccines. Discuss with
                 however, also contains the two genotypes that                                                           another pharmacist the ethical issues that
                 cause genital warts to encourage men to be                                                              may be associated with who (eg, adolescent
                 vaccinated — it is hoped that this will reduce                                                          girls, women, men) should get these
                 viral spread. Both vaccines include adjuvants.                                                          vaccines first.
                 Gardasil uses aluminium and Cervarox is for-
                 mulated with AS04.                                                                                   Evaluate
                    In anticipation of their launches ethical de-                                                     For your work to be presented as CPD, you need to
                 bate has already started to address who should                                                       evaluate your reading and any other activities.
                 get the vaccine first and how long it will take                                                      Answer the following questions: What have you
                 for these vaccines to be available in developing                                                     learnt? How has it added value to your practice?
                 countries, which account for 80 per cent of                                                          (Have you applied this learning or had any
                 the deaths from cervical cancer. Both Merck                                                          feedback?) What will you do now and how will this
                 and GSK say they will offer the vaccine at a                                                         be achieved?
                 discount to these countries.

212   The Pharmaceutical Journal (Vol 276) 18 February 2006                                                                               

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