VN October 2020

Vetnuus |Oktober 2020 30 Adjuvants andTheir Role inVaccines Regulars I Zoetis pages Immunology is a fascinating subject and vaccination is one of the most successful ways of preventing disease in both humans and animals. 1 The World Health Organisation (WHO) states that vaccination prevented 10 million (human) deaths between 2010 – 2015 and protected many additional millions of people from illness. 2 The public health benefits of vaccination (of humans and animals alike) could hardly be overstated and the recent COVID-19 outbreak underlined the devastating effects of infectious disease in an immunologically-naïve population. The Chinese used inoculation techniques to produce immunity against smallpox as early as 900 AD. 3 Inoculation is the method of transferring the actual disease-causing agent and thus inducing the disease and after recovery the individual would then be immune against the disease. This practice unfortunately resulted in many cases of severe disease and even mortalities. Edward Jenner is the first scientist to effectively develop vaccination, in that he induced immunity against smallpox in human patients that were experimentally infected with cow pox, the latter causing only mild clinical symptoms. 3 Since that first discovery, the scientific and medical world spent a lot of effort in the development of commercial vaccines. Early vaccines were generally live-attenuated or whole- pathogen preparations. Although some of these preparations are still being used today, concerns for safety and potential to cause disease, have directed the research towards subunit and inactivated vaccines. 3 This is especially true in human vaccines and less so in animal vaccines. Inactivated and sub-unit vaccines are generally less immunogenic than their modified live counterparts and benefit greatly from the use of adjuvants to ensure that adequate immunity develops upon administration. 4 This being said, the benefits of adjuvantation in modified live vaccines cannot be overlooked as they have the ability to enhance viral antigen immunogenicity. This is not to say that they do not have important benefits in modified live vaccines as well, especially if they have the ability to increase viral antigen immunogenicity. The word “adjuvant” is derived from the Latin word adjuvare , meaning “to help”. 5 Adjuvants are substances that, when given together with an antigen, enhances the rate, magnitude, format or quality of the immune response to that antigen. 6 Adjuvants have been improving vaccines for as long as vaccines have been used, for example the live viral inoculation of the early Chinese contained intrinsic adjuvants in the formof viral nucleic acid, the viral coat and possibly bacterial contamination. 7 The history of adjuvant discovery, however, starts with a French veterinarian named Gaston Ramon. While working at the Pasteur Institute in 1920, Ramon discovered that higher specific antibody titres were detected in horses that developed an abscess at the injection site. 1 He then replicated these results by inducing sterile abscesses (that resulted in inflammation at the injection site) with various substrates such as starch, breadcrumbs or tapioca. By significantly increasing antibody production with the addition of these non-specific inflammatory stimulants, he effectively discovered adjuvants. 6 In the same time- period, Alexander Glenny et al. discovered the immune enhancing effects of aluminium salts. 1 Aluminium salts were added to vaccines in 1932 and were the only licenced adjuvant in human vaccines for the following 70 years. Aluminium compounds still form the basis for most human vaccines. 6 Following the implementation of aluminium salt adjuvants, oil emulsions were shown to express highly effective adjuvant properties. Freund’s adjuvant is widely used in research and are formulated as Freund Incomplete Adjuvant (FIA) , a water-in-mineral oil emulsion or Freund Complete Adjuvant (FCA) that also contains heat killed mycobacteria. Although potent, Freund’s adjuvant is too reactogenic (with potential to cause injection site granulomas, abscesses or necrosis) to be utilised in commercial vaccines. 1,6 These scientists laid the foundational groundwork for adjuvant research and development, providing us with the variety of commercial adjuvants available today, as well as exciting research for future formulations. Although the bulk of vaccinology research goes into antigen determination and the development of new vaccines, adjuvant research is growing as scientists realise the important role they play in potentiating mammalian immune responses and subsequently enhancing vaccine efficacy. The last two decades have seen a lot of progress being made in the understanding of the mechanism of action of adjuvants, but a lot remains unclear and efficacy of these substances are often empirically derived. Zoetis Animal HealthPages FOR ANIMALS. FOR HEALTH. FOR YOU. Dr Schabort Froneman, Zoetis South Africa (Pty) Ltd, Technical Manager: Ruminants