4.4 Subunit vaccines
The risk of pathogenic reversion can be overcome if the vaccine contains only fragments (subunits) of the pathogen, but these must include critical antigens in order to provoke a protective immune response. Relatively few subunit vaccines fulfil these criteria, but they include the inactivated toxins (toxoids) of tetanus and diphtheria which have been in use for many years. A subunit vaccine against whooping cough (Acellular Pertussis Vaccine, APV) is under evaluation. Antigen preparations for use in vaccines have also been made from structural components of certain bacteria and viruses, for example, a surface antigen from the hepatitis B virus, or the coat polysaccharides of Neisseria meningitidis or Haemophilus influenzae.
Since the 1990s, a few highly successful conjugate vaccines have been produced, in which a subunit from the target pathogen is irreversibly bound in a ‘conjugate’ with bacterial proteins. The conjugate elicits a greatly enhanced immune response compared with the subunit alone. Several effective conjugate vaccines against H. influenzae type b (Hib) are already in use. In 1999, the UK was the first country to introduce the conjugate MenC vaccine against meningitis caused by Group C meningococci. The vaccine contains a Group C polysaccharide subunit antigen conjugated with either a harmless variant of diphtheria toxin or the tetanus toxoid. Trials are also underway of a conjugate vaccine against genital herpes which links a herpes virus glycoprotein subunit with lipid A, a component of the Gram-negative bacterial envelope.
The components of subunit vaccines have until recently been extracted and purified from cultures of intact pathogens by conventional biochemical techniques, but there is now increasing research into the genetic engineering of critical antigens. If the genes encoding these antigens can be identified and isolated, they can be inserted into the genomes of harmless bacteria or yeasts (genetic recombination). The expression of these genes can yield commercially useful quantities of pathogen-specific antigens as components of recombinant subunit vaccines, such as the current hepatitis B vaccine; others are being evaluated (e.g. against herpes simplex and human papilloma viruses).