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4 Strategies for vaccine production

4.1 Introduction

The type of antigen preparation used in active vaccines varies considerably, depending on the pathogen. For diseases such as tetanus, where a bacterial toxin causes the damage, the toxin is first chemically treated to turn it into a harmless toxoid, which is used as the immunising agent. Where protection is required against the pathogen itself, vaccines are based on whole organisms treated in some way to make them safe, or on complex mixtures of antigens taken from the infectious agent. In this section, we discuss the major production strategies for active vaccines, which conventionally contain one or a combination of:

  • intact killed pathogens;

  • live attenuated pathogens;

  • subcellular fragments or molecules from the pathogen – known as subunit vaccines – either alone or linked in ‘conjugates’ to other molecules.

Table 3 gives some examples of commonly used vaccines in each of these categories. The difficulties that can be encountered in developing an effective vaccine are well illustrated in Section 4.2 of the Cholera Case Study (see Section 4.2, which describes some of the many attempts to produce vaccines of all three types. Sometimes vaccine preparations consist of a mixture of components, as in one of the newer vaccines against cholera, which contains inactivated classical and El Tor bacterial strains and a component of the cholera toxin.

Table 3 Some examples of vaccine types.
Vaccine typeInfectious diseaseComments
killed or inactivated vaccinespolioSalk vaccine (IPV, see Polio Case Study in Section 1.5)
choleravarious combinations of El Tor, classical Inaba and Ogawa serotypes (see Cholera Case Study in Section 4.2)
influenzastrains vary annually
whooping coughkilled Bordetella pertussis
typhoidkilled Salmonella typhi
rabiesvarious strains with similar protection
live, attenuated vaccinestuberculosisBacillus Calmette Guérin (BCG
typhoidoral attenuated strain (Ty21a)
polioSabin oral vaccine (OPV, see Polio Case Study in Section 1.5)
choleraCVD103-HgR strain with attenuated El Tor strain
measles, mumps and rubellausually combined in MMR vaccine
yellow feversingle strain, stable for decades
chickenpoxattenuated varicella zoster (Oka strain)
subunit vaccinestetanustoxoid
choleratoxin A or B subunit (used in combination with killed or attenuated strains)
meningococcal meningitisGroups A and C surface polysaccharides; or conjugate vaccine (MenC)
typhoidcapsular polysaccharide (Vi)
pneumococcal pneumoniacombination of 23 variant surface polysaccharides
haemophilus influenzatype B capsular polysaccharide; or conjugate Hib vaccine
hepatitis Bsurface antigen

In addition, we will look briefly at a number of new approaches to vaccine design currently in development, including:

  • DNA vaccines containing ‘naked’ DNA encoding specific pathogen antigens;

  • Genetic engineering of genes coding for key pathogen antigens either as subunits, or for cloning into non-pathogenic infectious agents used as ‘gene vectors’ for expression in the vaccine recipient.