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.
SAGE
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?
GACVS
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.
WHO Smallpox Vaccine Emergency Stockpile
This document describes the WHO Smallpox Vaccine Emergency Stockpile (SVES) and the considerations and processes needed for countries to request vaccine in the event of a smallpox outbreak.
- Download the document
December 2017
Smallpox vaccine readings
Edward Jenner was the first to test a method to protect against smallpox in a scientific manner. He did his study in 1796, and although he did not invent this method, he is often considered the father of vaccines because of his scientific approach that proved the method worked.
The method Jenner tested involved taking material from a blister of someone infected with cowpox and inoculating it into another person’s skin; this was called arm-to-arm inoculation. However, by the late 1940s, scientific knowledge had developed enough, so that large-scale vaccine production was possible and disease control efforts could begin in earnest.
The next routinely recommended vaccines were developed early in the 20th century. These included vaccines that protect against pertussis (1914), diphtheria (1926), and tetanus (1938). These three vaccines were combined in 1948 and given as the DTP vaccine.
Late 1940s | Recommended Vaccines
Smallpox Diphtheria* Tetanus* Pertussis*
* Given in combination as DTP
The vaccine everyone was waiting for — polio vaccine
Parents were scared of the polio epidemics that occurred each summer; they kept their children away from swimming pools, sent them to stay with relatives in the country, and clamored for an understanding of the spread of polio. They waited for a vaccine, closely following vaccine trials and sending dimes to the White House to help the cause. When the polio vaccine was licensed in 1955, the country celebrated, and Jonas Salk, its inventor, became an overnight hero.
Late 1950s | Recommended Vaccines
Smallpox Diphtheria* Tetanus* Pertussis* Polio (IPV)
* Given in combination as DTP
More vaccines followed in the 1960s — measles, mumps and rubella
In 1963, the measles vaccine was developed, and by the late 1960s, vaccines were also available to protect against mumps (1967) and rubella (1969). These three vaccines were combined into the MMR vaccine by Dr. Maurice Hilleman in 1971.
Late 1960s | Recommended Vaccines
Smallpox Diphtheria* Tetanus* Pertussis* Polio (OPV) Measles Mumps Rubella
* Given in combination as DTP
The 1970s — vaccine success
During the 1970s, one vaccine was eliminated. Because of successful eradication efforts, the smallpox vaccine was no longer recommended for use after 1972. While vaccine research continued, new vaccines were not introduced during the 1970s.
Late 1970s | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Polio (OPV) Measles** Mumps** Rubella**
* Given in combination as DTP
** Given in combination as MMR
Vaccine development in the 1980s — hepatitis B and Haemophilus influenzae type b
The vaccine for Haemophilus influenzae type b was licensed in 1985 and placed on the recommended schedule in 1989. When the schedule was published again in 1994, the hepatitis B vaccine had been added.
The hepatitis B vaccine was not new, as it had been licensed in 1981 and recommended for high-risk groups such as infants whose mothers were hepatitis B surface antigen positive, healthcare workers, intravenous drug users, homosexual men and people with multiple sexual partners. However, immunization of these groups didn't effectively stop transmission of hepatitis B virus. That’s because about one-third of patients with acute disease were not in identifiable risk groups. The change of recommendation to immunize all infants in 1991 was the result of these failed attempts to control hepatitis B by only immunizing high-risk groups. Following this recommendation, hepatitis B disease was virtually eliminated in children less than 18 years of age in the United States.
1985 - 1994 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (OPV)
Hib
1994 - 1995 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (OPV) Hib Hepatitis B
* Given in combination as DTP
** Given in combination as MMR
Annual updates to the immunization schedule — 1995 to 2010
As more vaccines became available, an annual update to the schedule was important because of changes that providers needed to know, such as detailed information about who should receive each vaccine, age(s) of receipt, number of doses, time between doses, or use of combination vaccines. New vaccines were also added.
Important changes to the schedule between 1995 and 2010 included:
- New vaccines: Varicella (chickenpox - 1996), rotavirus (1998-1999; 2006, 2008); hepatitis A (2000); pneumococcal vaccine (2001)
- Additional recommendations for existing vaccines: influenza (2002); hepatitis A (2006)
- New versions of existing vaccines: acellular pertussis vaccine (DTaP ,1997); intranasal influenza (2004)
- Discontinuation of vaccine: Oral polio vaccine (2000)
2000 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (IPV) Hib Hepatitis B Varicella
Hepatitis A
2005 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (IPV) Hib Hepatitis B Varicella Hepatitis A Pneumococcal
Influenza
2010 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (IPV) Hib Hepatitis B Varicella Hepatitis A Pneumococcal Influenza Rotavirus
* Given in combination as DTaP
** Given in combination as MMR
The schedule from 2011 to Present
Annual updates to both the childhood and adult immunization schedules offer guidance to healthcare providers in the form of new recommendations, changes to existing recommendations, or clarifications to assist with interpretation of the schedule in certain circumstances. The schedules are reviewed by committees of experts from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians.
Important changes to the schedule:
- New vaccines: meningococcal serogroup B vaccine (2014)
- Additional recommendations for existing vaccines: HPV (2011 to routinely vaccinate males), intranasal influenza vaccine (2018 again recommended)
- Discontinuation of vaccine: intranasal influenza vaccine (2016)
2020 | Recommended Vaccines
Diphtheria* Tetanus* Pertussis* Measles** Mumps** Rubella** Polio (IPV) Hib Hepatitis B Varicella Hepatitis A Pneumococcal Influenza Rotavirus
* Given in combination as DTaP
** Given in combination as MMR
Combination vaccines
In the early 1950s, four vaccines were available: diphtheria, tetanus, pertussis and smallpox. Because three of these vaccines were combined into a single shot (DTP), children received five shots by the time they were 2 years old and not more than one shot at a single visit.
By the mid-1980s, seven vaccines were available: diphtheria, tetanus, pertussis, measles,mumps, rubella and polio. Because six of these vaccines were combined into two shots (DTP and MMR), and one, the polio vaccine, was given by mouth, children received five shots by the time they were 2 years old and not more than one shot at a single visit.
Since the mid-1980s, many vaccines have been added to the schedule. The result is that the vaccine schedule has become more complicated than it once was, and children are receiving far more shots than before (see Vaccine Safety for answers to the questions: "Are vaccines safe?"; “Do vaccines weaken the immune system?” and more). Now, children could receive as many as 27 shots by 2 years of age and up to six shots in a single visit. However, in the same way that the DTaP and MMR vaccines were combined, new combinations are being made to reduce the number of shots. Used in different age groups of children, the following combinations of vaccines are now available:
- Diphtheria, tetanus and acellular pertussis
- Diphtheria, tetanus, acellular pertussis, and inactivated polio
- Diphtheria, tetanus, acellular pertussis, inactivated polio and hepatitis B
- Diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenzae type b
- Diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type b, and hepatitis B
- Measles, mumps and rubella
- Measles, mumps, rubella, and varicella
- Hepatitis A and hepatitis B (only for those 18 years of age and older)
Vaccines for Adolescents: A new generation of vaccines
Adolescents, like adults, were recommended to get tetanus boosters every 10 years; most requiring their first booster dose around age 11. Other than this, however, most adolescents did not require additional vaccines unless they missed one in childhood. By 2005, vaccines specifically recommended for adolescents were only recommended for sub-groups based on where they lived or medical conditions that they had. However, a new group of vaccines became available in the latter part of the decade.
- New vaccines: Tdap, 2005, meningococcal conjugate (2005), HPV (2006 females, 2009 males), meningococcal serogroup B vaccine (2014)
- Additional recommendations for existing vaccines: HPV (2011 to routinely vaccinate males), intranasal influenza vaccine (2018 again recommended)
- New versions of existing vaccines: HPV (protecting against 9 types, 2015)
- Discontinuation of vaccine: intranasal influenza vaccine (2016)
2000
Recommended Vaccines
Td
Catch-up MMR Hepatitis B
Varicella
Sub-groups
Hepatitis A
2005
Recommended Vaccines
Tdap
Catch-up MMR Hepatitis B
Varicella
Sub-groups Hepatitis A Pneumococcus
Influenza
2010
Recommended Vaccines Tdap HPV Meningococcal conjugate (serogroups A,C,W,Y)
Influenza
Catch-up MMR Hepatitis B Varicella
Polio
Sub-groups Hepatitis A
Pneumococcus
2020
Recommended Vaccines Tdap HPV Meningococcal conjugate (serogroups A,C,W,Y) Influenza
Meningococcal serogroup B
Catch-up MMR Hepatitis B Varicella
Polio
Sub-groups Hepatitis A
Pneumococcus
Vaccines for adults — increasing opportunities for health
Historically, vaccines were deemed to be “only for children.” However, vaccines for adults are becoming increasingly common and necessary. Most adults think only of the tetanus booster recommended every 10 years and even then, many adults only get the vaccine if they injure themselves. In 2005, the Tdap vaccine was licensed as an improved version of the typical tetanus booster, Td. The newer version also contains a component to protect against pertussis (whooping cough). All adults, especially those who are going to be around young infants, should get the Tdap vaccine. Adults often unwittingly pass pertussis to young infants for whom the disease can be fatal. In 2012, the CDC recommended that pregnant women get a dose of Tdap during each pregnancy between 27 and 36 weeks’ gestation. In 2019, the CDC recommended that Tdap or Td vaccine could be used for booster dosing every 10 years.
Influenza vaccines, available since the 1940s, are now recommended for most adults. Vaccines like MMR and chickenpox are recommended for adults who have not had the diseases, and vaccines including hepatitis A, hepatitis B, pneumococcus, and meningococcus are recommended for sub-groups of the adult population. The HPV vaccine became available in 2006. In 2018, the license was expanded to include people up to 45 years of age.
The first shingles vaccine, Zostavax®, was licensed in 2006; a second shingles vaccine, Shingrix®, licensed in 2017, produces a more robust immune response than Zostavax did. Two doses of this vaccine, separated by two to six months, are recommended for people 50 years and older. In 2019, Zostavax was no longer available.
In late 2020, the first COVID-19 vaccines were approved for use in response to the COVID-19 pandemic. Most adults were recommended to get this vaccine, but limited supplies required adults to be assigned to eligibility groups in order to protect those most at risk first.
Unlike childhood vaccines, which are often required for entrance to schools, adult vaccines are typically not mandated. However, people with certain occupations may be required to get vaccinated as a condition of employment. Most often, this occurs in the military and in healthcare-related occupations, but other industries may also require employment-based vaccinations. Limited requirements and a lack of preventive healthcare by most adults have led to low levels of vaccine use by adults.
The first formal adult immunization schedule was published in 2002 and is updated annually.
Learn more about the vaccine schedule for adults.
Reviewed by Paul A. Offit, MD on March 30, 2021
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