Another major contribution to the development of vaccines in the early 1920s came with the discovery that certain substances could increase yields of immune sera containing antitoxins. The research carried out by Alexander Glenny and Gaston Ramon was primarily intended to increase the yields of hyperimmune sera produced in animals such as horses, rather than to increase the active immune response after antigenic stimulation in humans. Y27632 Ramon noted that horses that spontaneously developed abscesses at the injection site produced

greater serum antitoxin titres. Subsequently, he successfully described a group of substances, ranging from starch, bread crumbs and tapioca (used because they contained starch), which, when injected in conjunction with toxoids, enhanced the immune response. These substances were tested because it was already known that they caused aseptic abscesses/inflammation.

The term adjuvants, from the Latin adjuvare (‘to help or to aid’), was coined by Ramon to describe these substances. Around the same time, aluminium salts were tested by Glenny (1926) to increase the immune response to the diphtheria toxoid in horses and, shortly after, in humans. GSK2126458 Today, 80 years later, aluminium salts still remain the most commonly used adjuvant in vaccines (see Chapter 4 – Vaccine adjuvants). In 1931, Ernest Goodpasture introduced the use of embryonated hen’s eggs as a medium for growing viruses. This technique represented a major advance since, until its introduction, human viruses could only be grown in animals such as ferrets and mice. The chick embryo proved to be a cheaper and safer medium for the culture of viruses. Using the egg system, Max Theiler at The Rockefeller Foundation developed an effective vaccine for yellow fever in the 1930s and received the Nobel Prize in Medicine in 1951. Vaccines against typhus that were important enough for troops in World War II were also developed during the 1930s. The first influenza vaccine was developed in 1940, and was a live, attenuated virus produced in hen’s eggs. However, due to the instability of the viral genome, the viruses mutated rapidly and were not attenuated consistently, causing outbreaks of disease in

vaccinees, which led to the discontinuation of the product for safety reasons. In 1906, Albert Calmette and Albert Guérin started to culture Mycobacterium bovis bacillus in a potato medium to which glycerin and beef bile were added to strip the lipids from the waxy capsule of the microorganism. After 13 years and 230 passages through the medium, they obtained an attenuated strain, bacillus Calmette–Guérin (BCG). The first BCG vaccine became available in 1927 and is still widely used for the prevention of disseminated TB and TB meningitis in children. During the 1930s, the use of animal cell cultures to grow pathogens became available. This important new technology for the development of vaccines replaced the practice of deliberate animal-to-animal transmission of infection.