Vaccines are an antigenic preparation used to produce active immunity to a disease and may be classified in the following way. (See also Table 1.2.)
To produce a live vaccine, such as MMR or varicella, the wild or disease-causing virus is attenuated (weakened), traditionally by repeated culture in the laboratory, or nowadays for new live vaccines, by genetic engineering, such as with rotavirus vaccines. The virulence properties of the virus are reduced so that it does not cause disease in healthy individuals. The attenuated vaccine virus multiplies to a limited extent in host tissue and induces an immune response similar to wild virus infection in the majority of subjects. Live vaccines are generally very effective and induce long-lived immunity.
In some instances (eg, varicella vaccine in adults), more than one dose may be needed because effective replication of the vaccine virus, and hence immunity, does not always result from the ﬁrst dose.
The term ‘killed’ is generally used for bacterial vaccines and the term ‘inactivated’ for viral vaccines. These vaccines are prepared by treating the whole cell or virus with chemicals that cause inactivation. Generally these organisms remain intact and whole. They generate an immune response (to a broad range of antigens) but cannot cause an infection because they are dead and so cannot reproduce.
Subunit vaccines are developed using only the antigens known to elicit protective immunity. They can be further categorised as follows.
In some bacterial infections (eg, diphtheria, tetanus), the clinical manifestations of disease are caused not by the bacteria themselves but by the toxins they secrete. Toxoid vaccines are produced by harvesting a toxin and altering it chemically (usually with formaldehyde) to convert the toxin to a toxoid. The toxoid is then purified. Toxoid vaccines induce antibodies that neutralise the harmful exotoxins released from these bacteria.
Recombinant vaccines, such as those used against hepatitis B and HPV, are made using a gene from the (disease-causing) pathogen as an antigen, which generates a protective immune response. The gene is inserted into a cell system capable of producing large amounts of the protein of interest. For example, the gene for the hepatitis B surface antigen is inserted into yeast cells, which replicate and produce large amounts of the hepatitis B surface antigen. This is purified and used to make vaccine. The advantage of this approach is that it results in a very pure vaccine that is efficient to produce.
Polysaccharides are strings of sugars. Some bacteria, such as Streptococcus pneumoniae and Neisseria meningitidis, have large amounts of polysaccharide on their surface, which encapsulate the bacteria. The polysaccharide capsules protect the bacteria from the host’s immune system and can make the bacteria more virulent. Historically, it has been difficult to stimulate an effective immune response to these polysaccharide capsules using vaccines, particularly in children aged under 2 years.
First-generation capsular polysaccharide vaccines contained antigens isolated from the different polysaccharide capsules (eg, 4vMenPV and 23PPV, see chapters 12 and 15). Polysaccharide vaccines are poorly immunogenic. They produce low affinity antibodies (which do not bind well to the antigen) and, because they do not elicit T-cell responses, immune memory does not develop. Multiple priming doses (even a single dose) can cause hyporesponsiveness in both children and adults to further doses (see section 12.4.2).
The new generation conjugate vaccines (eg, PCV13 and MCV4-D) contain carrier proteins that are chemically attached to the polysaccharide antigens. Attaching relatively non-immunogenic polysaccharides to the highly immunogenic carrier proteins means that by activating a T-cell response, conjugate vaccines induce both high-affinity antibodies against the polysaccharide, and immune memory.
Examples of carrier proteins and vaccines that use them are:
The new generation conjugate vaccines are limited by the number of polysaccharides that can be covalently linked to the carrier molecule, so there is still a role for polysaccharide vaccines to broaden the number of serotypes recognised. For example, PCV13 has 13 serotypes, compared to 23PPV with 23 serotypes. Conjugate vaccine technology is expected to improve, so that polysaccharide vaccines can eventually be phased out.
Another subunit vaccine is acellular pertussis vaccine, which is prepared from purified fragments of Bordetella pertussis. Outer membrane vesicle vaccines (OMV), such as the meningococcal B vaccines, are made from ‘chunks’ of the outer membrane of the cell. They contain a range of antigens.
|Live attenuated||Inactivated or whole killed||Subunit|
|Poliomyelitis (IPV) |
Some influenza vaccines
Note: Travel vaccines have been omitted from the above table.