Vaccination is the most efficient and effective method of controlling infectious diseases ever developed. The enormous improvements in human health through the twentieth century and beyond have been, in large part, a result of the development of effective vaccines. Likewise, many of the improvements in animal health, especially the great increases in productivity resulting from effective disease control are a direct result of vaccine use. The eradication of smallpox in humans as well as the elimination of rinderpest in cattle are both directly the result of effective vaccination campaigns. The early history of veterinary vaccines can be divided into four stages. The first stage was the discovery of variolation against human smallpox and its eventual evolution into vaccination. The second stage was launched by the discoveries of Louis Pasteur and his colleagues that led to the early production of numerous effective vaccines against predominantly bacterial diseases. The third stage, typified by the development of the canine distemper vaccines, was a process of progressive improvement of these vaccines and resulted from a growing knowledge about viruses and their behavior. Finally, the sophisticated use of vaccines has led to the elimination of two major diseases, smallpox and rinderpest, and the near eradication of others. The earliest record of protective immunity dates from 430 BCE, when the Greek historian Thucydides describing the plague of Athens (of unknown cause) observed “… for no one caught the disease twice, or, if he did, the second attack was never fatal.” Sometime before the fifteenth century, the Chinese also observed that those individuals who recovered from an attack of smallpox never suffered from it a second time. It was a small step therefore to attempt to protect children from the disease by deliberately infecting them. Initially the process involved blowing dried scab powder up the nose of infants. Eventually however, improved results were obtained by placing the dried scabs in a small incision in the arm. The resulting local disease was less severe and mortality correspondingly lower. Descriptions of this technique spread westward along the Silk Road until it eventually reached the Ottoman Empire—modern Turkey. It was widely employed across the Middle East. Reports of this technique called “variolation,” eventually reached England in the early 1700s. One such example came in 1714 by way of a letter from a physician, Dr. Emanuel Timoni, who practiced medicine in Constantinople. In addition, first-hand reports from Lady Mary Montagu, the wife of the English Ambassador to Constantinople impressed the people who mattered. Lady Montagu arranged to have her own son successfully variolated through Dr. Timoni. Voltaire described her as “[a] woman of so fine a genius, and endued with as great a strength of mind, as any of her sex in the United Kingdom.” These reports were taken seriously because the Prince of Wales (the future King George II) and his wife were terrified that smallpox would attack their grandchildren. As a result, the process was investigated by variolating prisoners in London’s Newgate Prison. When this “Royal Experiment” proved to be successful, variolation was rapidly adopted in England. Around the same time (1721) variolation was successfully used by Dr. Zabdiel Boylston in Boston who had read Timoni’s letter. Although the technique worked, it was still accompanied by significant morbidity and some mortality, so it was not universally adopted in the American colonies. Some believed that diseases such as smallpox were God’s punishment for sins so that variolation was obviously in conflict with God’s will and thus inappropriate. Variolation clearly worked; however, nobody at that time had any concept as to how it might induce immunity to smallpox. Nevertheless, attempts were made to replicate the technique in other diseases. The most significant of these attempts resulted in the discovery of vaccination. In 1768, John Fewster, a physician in Gloucestershire, in the west of England, and his colleagues began to inoculate their patients against smallpox. They found however that many patients did not react to variolation. Upon inquiry, Fewster found that these patients had previously been infected with cowpox. Fewster reported his observations to the local Medical Society, but he did not fully recognize its significance and never published his findings. Among the Society’s members was a young apprentice called Edward Jenner. In 1774 an English farmer, Benjamin Jesty, performed the first documented substitution of cowpox for smallpox. He obtained the scab material from a cow of a neighbor and inoculated his wife in the arm under her elbow. He never wrote an account of this and he did not determine if she was immune. The widespread acceptance of this method did not come for another 24 years. In the 1790s, Edward Jenner was still working as a physician in the west of England, and he remembered Fewster’s observation. He also recognized that deliberate inoculation of cowpox could confer immunity against smallpox. Cowpox, otherwise known as vaccinia (vacca is Latin for cow), is a virus-mediated skin disease of cattle. Affected animals generally develop a large weeping ulcer on hairless skin such as the udder. When these infected cattle are hand milked, the vaccinia virus can readily enter cuts or abrasions on the milker’s hands. Humans infected by this virus develop a localized weeping lesion that scabs over and heals within a few weeks. We now know that the cowpox virus triggers a powerful immune response. Most importantly, however, vaccinia virus is closely related to smallpox virus to such an extent that these individuals also develop immunity to smallpox. Edward Jenner began a systematic study of the protective effects of vaccination and published his results in 1798. The scientific method was not well established in the late eighteenth century. Thus Jenner published a series of case reports on vaccination. This drew immediate attention because the method worked well and was clearly very much safer than variolation (Box 1.1). Despite some initial opposition, the principal physicians and surgeons of London supported Jenner, and, as a result, vaccination was rapidly adopted in Europe and the Americas, whereas variolation was discontinued (Fig. 1.1). Jenner quite properly received credit for publishing the vaccination process, but his biographer invented a myth that Jenner alone had discovered the process by talking to a dairymaid. In fact, this protective effect of vaccination was independently recognized in several other English and European communities. It must be emphasized that Jenner had no concept of microbiology, viruses, or immunity. For example, he did not know where smallpox came from. He noted, however, that the disease occurred in farms where there were both cattle and horses. The same workers looked after both, and he suggested that they transmitted cowpox from horses to cattle. Jenner therefore believed that the skin disease of horses colloquially called “the grease” was the source of cowpox. He likely confused this disease with horsepox. However, he clearly believed that horses were the original source of cowpox, and as a result he obtained some of his vaccine material from horses. Horsepox, which like other poxviruses caused multiple skin lesions, was a common disease of horses at that time. Jenner continued to believe in “equination,” and in later years tended to prefer the use of equine material to cowpox. Subsequent to Jenner’s discovery, the British government decided to vaccinate all their soldiers. The contract to produce this vaccine was given in 1801 to a Dr. John Loy who used material from horses exclusively. In 1803 an Italian physician, Dr. Luigi Sacco, read a book by Dr. Loy and also used equine “grease” with great success in children. Although cowpox was the preferred material for vaccination through the nineteenth century, equine material was used on occasion. It is likely that at least some of the vaccinia stocks used in humans were of equine origin. Vaccinia virus as currently used differs significantly from circulating cowpox virus strains. Although horsepox has become almost extinct, it has been possible to examine the genome of a Mongolian strain of horsepox. This is also related to but distinct from vaccinia. Several horsepox genes are present in different vaccinia strains, whereas some vaccinia strains appear to be more closely related to horsepox than to cowpox. Although physicians (and veterinarians) were totally unaware of how vaccinia worked, it did not stop them from seeking to use this methodology to prevent other diseases. Many believed vaccinia to be an effective treatment for unrelated diseases in humans including the plague and cholera. Cattle plague (rinderpest) was a major devastating disease in Europe until the end of the nineteenth century when it was eliminated by movement control and slaughter. We now know it was caused by a morbillivirus related to human measles. However, in the eighteenth century many of those who encountered cattle plague considered that it was very similar to smallpox. Thus once variolation (inoculation) was introduced into Europe in 1717, numerous individuals attempted to prevent cattle plague by inoculating healthy cattle with material from plague-affected cattle. One such method involved making an incision in the dewlap and inserting a piece of string that had been soaked in nasal or ocular discharge. This was removed after 2 to 3 days. It was claimed that animals sickened and then recovered. A booklet was published in 1757 recommending this procedure, and it was widely adopted in England. However, it was eventually recognized that all such attempts were not effective and killed a lot of cattle. Despite this, widespread attempts to inoculate cattle against rinderpest were conducted in Denmark, the Netherlands, and what is now Germany. By 1770 most had been abandoned. In 1774, an adaptation of the vaccination procedure was tested in the Netherlands by Geert Reinders, a farmer from Groningen. He had noticed that calves from recovered cows appeared resistant to reinfection. This may have been the first recognition of the phenomenon of maternal immunity. Reinders made use of this resistant period to inoculate 6- to 8-week-old calves with nasal material from recovered cows. He also observed that he got better results if he repeated the inoculation of these calves two more times. Reinders was criticized by those who believed that disease was a manifestation of God’s will. More importantly, his was not a practical procedure and fell into disuse. Reinders success encouraged others to pursue other methods of inoculation against cattle plague and it was widely employed across northern Europe. In 1780 the Amsterdam society for the Advancement of Agriculture reported that of more than 3000 animals inoculated, 89% had survived as opposed to 29% survival in uninoculated animals. As a result, more than half the cattle were inoculated in some regions of the Netherlands. As the results of inoculation gradually improved, an argument developed between those that believed inoculation to be the solution to the cattle plague problem and those who believed that prompt slaughter was a more effective control procedure. Over the course of the nineteenth century, slaughter gradually superseded inoculation as a control method in Europe. This disease was a major problem in Europe through the nineteenth century and inoculation was first attempted in England and Germany at that time. However, credit is usually given to Louis Willems of Hasselt in Belgium, who in the early 1850s inoculated lung fluid from affected animals into the tail of recipient cattle. He used a large lancet dipped in the fluid and used this to make two to three incisions at the tip of the tail. It caused large abscesses, the animals sickened and recovered, the tail commonly fell off (the Willems reaction), but the animals became immune (Fig. 1.2). Several European governments formed commissions to look into Willems claims and confirm its effectiveness. The Dutch reported that untreated cattle had 35% mortality. In vaccinated animals 8% to 10% had severe reactions with 1.1% mortality. Use of this vaccine became widespread, but it was eventually replaced with modern live attenuated vaccines, which can also cause severe reactions.
A brief history of veterinary vaccines
Variolation and vaccination
Edward Jenner
Cattle plague
Contagious bovine pleuropneumonia
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