This was an extension of the toxoid approach, which many years earlier showed that it was unnecessary to include the whole organism in some vaccines. By eliminating any unwanted pathogenic components like lipids and nucleoproteins,

the high purity of these antigens resulted in vaccines with reduced reactogenicity and improved safety profiles. The subunit approach utilises selected and purified single proteins or antigens, such as pertussis proteins, which form the acellular vaccine, or pneumococcal polysaccharides. In general, split and subunit vaccines are less reactogenic compared with the whole Selleckchem Ku 0059436 pathogen but, in many instances, they also have reduced immunogenicity. In the early 1980s, the recombinant protein concept, built on advances in genetic engineering from the 1970s onwards, enabled a further technological leap in vaccine development. In this technique, a section of DNA coding for an antigenic protein is inserted into an expression system and the protein encoded is produced in large quantities. The recombinant proteins are harvested and purified from the expression system for incorporation into the vaccine. The recombinant approach excels at achieving non-infectious, highly pure antigen; in addition, it allows the production of antigens in large quantities

so providing more doses. The first hepatitis B virus (HBV) vaccine was developed in 1970 by a 3-fold inactivation of HBV in plasma from the blood of chronic HBV carriers Vincristine solubility dmso (see Chapter 3 – Vaccine antigens).

Particles of hepatitis B surface antigen found in their plasma were immunogenic and protective as a vaccine and did not cause infection. The first plasma-derived HBV vaccine was manufactured in 1981 with a very good safety record, but despite extensive purification measures to inactivate any potential contaminating fantofarone agents, physicians and the general public were very reluctant to use a product that carried even a remote theoretical risk of contamination with blood-borne agents. Moreover, as the vaccine depended on human serum from chronic carriers, sources of antigen were limited. These obstacles prompted the formulation of the first recombinant vaccine; an HBV vaccine that was as effective as the plasma-derived vaccine was licensed in 1986. This used the purified recombinant HBV surface antigen produced in a yeast expression system. Since 2006, two additional recombinant vaccines have been made available. These prevent infection with human papillomavirus (HPV) types that cause cervical cancer (HPV-16, HPV-18), and one of the vaccines also prevents infection with HPV types causing genital warts (HPV-6, HPV-11). The vaccines consist of immunogenic virus-like particles (VLPs) prepared from recombinant HPV L1 coat protein in yeast, or insect cells. The coat proteins self-assemble during the purification process and mimic the overall structure of virus particles, but contain no HPV nucleic acid and cannot cause infection.