The history of smallpox holds a unique place in medicine. It was one of the deadliest diseases known to humans, and to date (2016) the only human disease to have been eradicated by vaccination. The smallpox vaccine, introduced by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that inoculated vaccinia protected against inoculated variola virus.
The global eradication effort initially used a strategy of mass vaccination campaigns to achieve 80% vaccine coverage in each country, and thereafter by case-finding, followed by ring vaccination of all known and possible contacts to seal off the outbreak from the rest of the population.
In 1961 the bifurcated needle was developed as a more efficient and cost effective alternative, and was the primary instrument used during the eradication campaign from 1966 to 1977. The bifurcated needle vaccination required only one-fourth the amount of vaccine needed with previous methods and was simpler to perform.
Different types of vaccine
Smallpox vaccines produced and successfully used during the intensified eradication program are called first generation vaccines in contrast to smallpox vaccines developed at the end of the eradication phase or thereafter and produced by modern cell culture techniques. Second generation smallpox vaccines use the same smallpox vaccine strains employed for manufacture of first generation vaccines or clonal virus variants plaque purified from traditional vaccine stocks, whereas third generation smallpox vaccines represent more attenuated vaccine strains specifically developed as safer vaccines at the end of the eradication phase by further passage in cell culture or animals. Second and third generation vaccines are produced using modern cell culture techniques and current standards of Good Manufacturing Practices (GMP).
The need for WHO to maintain an emergency reserve of smallpox vaccine following eradication was recognized in 1980 when WHO was given a set of formal responsibilities for maintaining capacity and expertise to respond to a re-emergence of smallpox in the post-eradication era as both a component of a preparedness strategy and a possible deterrent to intentional release. The Smallpox Vaccine Emergency Stockpile (SVES) was originally created by consolidating WHO Member State donations given in support of the Intensified Smallpox Eradication Programme.
In 2002, World Health Assembly (WHA) Resolution 55.16 urged Member States to share expertise, supplies and resources to rapidly contain a public health emergency or mitigate its effects. The resolution further requested the WHO Director General to examine the possible development of collaborative mechanisms to prepare and stockpile resources for a potential PHEIC. The SVES currently consists of two components:
A physical stockpile of vaccine held by WHO Headquarters in Switzerland, which is composed of calf-lymph smallpox vaccines from a variety of sources dating from the final years of the eradication program that are regularly tested for potency. It is estimated to consist of approximately 2.4 million doses when reconstituted and delivered by bifurcated needle.
A pledged stockpile held by Donor countries in their respective national stockpiles for use in time of international need upon request by WHO, which currently consists of 31.01 million doses of smallpox vaccine held by France, Germany, Japan, New Zealand, and the United States.
Given the different set of vaccines available (1st generation vaccines used during the eradication campaign and made from the lymph or skin of inoculated animals, 2nd generation vaccines produced in tissue cells and further attenuated, and 3rd generation vaccines based on replicating or non-replicating virus) WHO needs to be able to make an informed decision on which vaccines to include in the stockpile for use in case of a re-emergence of smallpox. Therefore, Strategic Advisory Group of Experts on immunization (SAGE) was asked to respond to the following questions: Which vaccine should be recommended for use during an outbreak of smallpox and how many doses should be stockpiled? What groups should be targeted for vaccination if an outbreak occurs? Which groups should be vaccinated for preventive use and with which vaccine?
The Global Advisory Committee on Vaccine Safety (GACVS) was requested to review the safety of smallpox vaccination. The Committee was provided with updated safety information for 1st, 2nd and 3rd generation smallpox vaccines in order to make informed decisions regarding emergency smallpox vaccine stockpiling and future use. The safety update also included an overview of the safety of smallpox vaccines used in the smallpox eradication efforts.
Smallpox vaccine readings
Smallpox vaccine: The Good, the Bad, and the Ugly
Recommendations for the production and quality control of smallpox vaccines, TRS 926
Best Practices in Vaccine Production for Smallpox and Other Potential Pathogens