Vaccinations
Vaccinations are arguable the most important advance in medicine in the previous 350 years. In terms of lives saved and reduction in morbidity, no other intervention comes close to the effectiveness of vaccination programs.
Obviously, vaccination depends on the concept of immunological memory that is part of the adaptive immune response. Vaccines produce both T- and B-memory-cells and hence are effective against a wide range of pathogens. The natural course of events is that an individual will have one exposure to a pathogen and then (if they survive) will be immune to that pathogen. The idea of vaccination is to provide the pathogen’s antigens is a safe form so that without getting ill the individual is henceforth protected.
Edward Jenner (1749-1823) is credited with the invention of vaccination. Jenner had observed that people infected with cowpox were resistant to smallpox. Smallpox is a horrific and deadly disease whilst cowpox is slightly unpleasant. Jenner demonstrated that exposure to cowpox protected a person from smallpox. The term vaccination stems from the Latin for cow vacca in honour of Jenner’s work. In an age when the nature of infection was not understood his work is remarkable and on the 8th May 1980 the WHO was able to announce that smallpox had been successful eradicated. It remains the only viral disease that has been completely eliminated although there is an on-going effort to eradicate polio. Smallpox vaccine is very unusual in that the cowpox and smallpox viruses have an antigen that is sufficiently similar to provide protection; the immune response to cowpox is also effective against smallpox. For most other vaccines it has been necessary to engineer the pathogen in some way in order to produce an antigen that will stimulate the immune system.
There are essentially three ways to produce a vaccine.
Live attenuated vaccines: i.e. Polio
Subunit vaccines: i.e. Hepatitis B
Inactivated pathogens: i.e. Hepatitis A
The live attenuated vaccines tend to be the most effective, probably because they recruit a larger number of lymphocytes to the immune response and thus a greater number of memory cells are formed. Some vaccines, such as tetanus do not actually provide resistance to the infective organism but to its toxin. The pathogenesis of tetanus is via the tetanus toxin that the bacterium releases. The tetanus toxoid is a modified form of this protein and thus it induces an antibody response but is totally safe. Subsequent infection with Clostridium tetani will not give rise to tetanus because the immune system is able to ‘mop-up’ the toxin.
The table shows some of the commonly used vaccines, what type they are, how they are administered and when.
|
Vaccine Given |
Type |
Administration |
When given |
|
Hepatitis A |
Inactivated |
Intra-muscular injection |
Travel |
|
Hepatitis B |
Sub-unit |
Intra-muscular /
sub-cutaneous |
At-risk individuals (i.e.
health professionals) |
|
Measles |
Attenuated |
Given as MMR (trivalent
vaccine) Intra-muscular injection |
13 months old. Booster between 3 years 4
months and 5 years |
|
Mumps |
Attenuated |
||
|
Rubellla |
Attenuated |
||
|
Polio |
Inactivated / (attenuated) |
Intra-muscular / (oral) |
Given as one injection with
diphtheria, tetanus, pertussis and Hib at 2, 3 and 4 months of age. Booster
given orally at 3-5 years and 15-18 years |
|
Meningitis C |
Sub-unit / conjugate |
Intra-muscular |
2, 3 and 4 months of age |
|
Diptheria |
Sub-unit (toxoid |
Given as one injection |
2, 3 and 4 months of age. Booster between 3 years 4
months and 5 years |
|
Pertussis |
Sub-unit |
||
|
Tetanus |
Sub-unit (toxoid) |
||
|
Haemophilus influenzae B
(Hib) |
Sub-unit |
||
|
BCG |
Attenuated |
Intra-muscular |
10-14 years (sometimes
earlier in at-risk groups) |
|
Pneumococcal |
Sub-unit |
Intra-muscular |
At-risk groups |
Conjugate Vaccines: Hib and Meningitis C
Both Hib and meningitis C vaccines are conjugate vaccines. The original vaccines were made from polysaccharides that are found on the bacterial surface. These do produce an immune response but the production of memory B cells is very poor. The reason for this lies in the T-cell dependent manner in which B-lymphocytes produce memory cells.
Having bound antigen, B-lymphocytes process that antigen and present it to T-helper cells. The T-helper cell is very important in producing memory cells and isotype switching of the B cell (as described in the section on T-helper cells). B-lymphocytes are able to bind to protein and polysaccharide antigens, however T-helper cells only respond to protein antigens. As a consequence the polysaccharide vaccines had only limited effectiveness.
Conjugate vaccines solve this problem by joining (conjugating) the polysaccharide antigen to a protein that the immune system can recognise such as tetanus toxoid. B-cells that recognise the N. meningitidis polysaccharide will then process and present the protein antigen to a T-helper cell. This triggers the production of memory B cells and isotype switching. If ever exposed to the antigen again, the memory B-cells are therefore present and able to mount an effective immune response.
Herd Immunity
The concept of herd immunity is very important in immunisation. In any population, not all individuals will be immunised and some will have the vaccination but will not respond well to it. This does not mean that they have no protection. Infectious diseases are by their very nature transmitted from one individual to another. If a sufficiently large number of individuals are resistant to an infection then it disappears in that population. An infected individual, if the immunisation rates are high enough will not encounter any one who is susceptible and thus when that individual either dies or recovers the disease disappears. As a consequence of this principal, small pox was eradicated worldwide and many other diseases, such as polio and measles, have been erased from some populations. Although if immunisation rates fall, these diseases re-emerge. It is generally estimated that a vaccine uptake rate of around 90% is required to protect the whole population.
