History of Vaccinations and Vaccines

Vaccines have changed the course of human history. Prior to their discovery, infectious diseases caused disability and death to countless adults and children who did not have the immune defenses to fight them.

By exposing them to substances that provoked a robust immune response, vaccinated people were largely shielded from either getting or experiencing severe illness from these otherwise deadly infections.

The first vaccines, introduced in the 18th and 19th centuries, ushered in an era during which scientists gained a greater understanding of the immune system and ways to stimulate the production of disease-fighting cells, called antibodies.

Armed with these insights, scientists today have been able to create novel vaccines that induce this response in many different ways, including technologies that led to the development of COVID-19 vaccines. In some cases, the building of herd immunity in vaccinated populations has led to the total eradication of certain diseases that once killed millions.

18th and 19th Centuries

The concept of vaccination and immunization far preceded what is generally consider to be the "age of vaccines."

Even as far back as the 11th century, historical records have shown that the Chinese practiced variolation, a technique by which tiny amounts of pus from people with smallpox were introduced into the bodies of those without it. By doing so, people exposed to only small amounts of the virus were largely shielded from the ravages of the disease. However, some did get sick and even died.

But, the actual development of vaccines—substances that provide immune protection without minimal risk of disease—only started around the turn of the 18th century.

Among the seminal moments in early vaccine history:

• Edward Jenner develops the first vaccine against smallpox in 1796. He found that by inoculating people with cowpox, a similar virus that only causes mild illness, they were largely immune to the effects of the more deadly disease.
• Louis Pasteur develops a vaccine for rabies in 1885 after having produced the first laboratory vaccine for chicken cholera in 1879. For the rabies vaccine, Pasteur used a live attenuated (weakened) virus to provoke an immune response.
• A cholera vaccine is developed by Spanish physician Jaime Ferrán in 1885—the first such vaccine to immunize against a bacterial disease in humans.
• A vaccine for typhoid is developed in 1896 by scientists Richard Pfeiffer and Wilhelm Kolle using whole killed (inactivated) bacteria.

1900 to 1979

The early 20th century was marked by rapid advances in vaccine research, due in large part to the technologies that allowed scientists to isolate and distinguish between different viruses or bacteria. This enabled scientists to differentiate, for example, measles from smallpox—a discovery only made in 1900 by the Persian scientist Rhazes.

Among the key vaccine achievements of the early- to mid-20th century:

• The first diphtheria vaccine is developed in 1913 through the work of Emil Adolf von Behring (of Germany), William Hallock Park (of the United States), and other scientists.
• The first whole-cell pertussis (whooping cough) vaccines are developed in 1914, although it will take several decades before they are widely used.
• The first successful tetanus vaccine is developed in 1927 based on research von Behring conducted in the 1890s.
• Max Theiler develops the first yellow fever vaccine in 1936.
• The first influenza vaccine is licensed for use in 1945. Scientists Thomas Francis Jr. and Jonas Salk were among the scientist who spearheaded the development of this inactivated, whole-virus vaccine.
• Individual diphtheria, tetanus, and pertussis vaccines are combined in a single DTP vaccine in 1948. It is the first instance in which vaccines are combined to ease the burden of vaccination in children and adults.
• Salk develops the inactivated polio vaccine (IPV) in 1955.
• A live, oral polio vaccine (OPV) developed by Albert Sabin replaces the Salk vaccine in 1962.
• The first live attenuated measles vaccine is developed by John Enders in 1963, of which 19 million doses are distributed over the next 12 years.
• In 1967, the mumps vaccine is developed by Maurice Hilleman, of which 11 million doses are distributed within the next five years.
• Maurice Hilleman also leads the development of the rubella (German measles) vaccine, licensed for use in 1969.
• The combined measle, mumps, and rubella (MMR) vaccine is licensed for use in 1971.
• Pneumovax, the first pneumococcal vaccine to protect against certain types of Streptococcus pneumoniae, is approved in 1971. It is still used today in high-risk children.
• Virus elimination: In 1979, smallpox is the first disease declared eliminated by the World Health Assembly. The last case involved a Somalian man with a very mild form of the disease in 1977.

From 1980 to 2000

With the eradication of smallpox in 1979, scientists aimed to achieve the same with a host of other diseases. Aiding them in this quest were rapid advances in technology that allowed researchers to look closely at the mechanisms that induce an immune response—right down to a cell's genetic sequence.

Among the achievements of the latter part of the 20th century:

• Menomune, the first meningococcal vaccine, is licensed for use in 1981 and quickly becomes the standard of preventive care in high-risk children until it is replaced by Menactra in 2005.
• A hepatitis B vaccine is licensed in 1981 and becomes the first subunit vaccine to induce a protective immune response with only a piece of the hepatitis B virus.
• The first recombinant hepatitis B vaccine, called Recombivax HB, is approved in 1986. Unlike traditional vaccines that use a live or killed organism to trigger an immune response, recombinant vaccines insert DNA into cells to encode instructions on how to build disease-specific antibodies.
• The first Haemophilus influenza type b (Hib) vaccine is licensed for use. It is classified as a conjugate vaccine that combines two different antigens (in this case, inactivated Hib with proteins from another infectious bacteria) to induce a more robust immune response.
• In 1989, to speed the eradication of measles, a booster dose of MMR is recommended for children who live in counties that have at least five cases.
• In 1993, the first quadrivalent (four-in-one) combination vaccine called Tetramune, combining the DTP and Hib vaccines, is approved. Subsequent combinations include Pediarix (DTaP, polio, hepatitis B) in 2004, ProQuad (MMR, varicella) in 2006, Pentacel (DTaP, polio, Hib) in 2008, Kinrix (DTaP, polio) in 2008, and Vaxelis (DTaP, polio, hepatitis B, Hib) in 2018.
• Virus elimination: In 1994, the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) declare that polio has been eliminated from the Western Hemisphere.
• The first varicella (chickenpox) vaccine, called Varivax, is licensed for use in the United States in 1995 (although vaccination for the disease had already commenced in Japan and Korea as early 1988).
• The first hepatitis A vaccine, called VAQTA, is approved for use in 1996.
• In 1996, the Salk polio vaccine is once again recommended for use due to the small risk of vaccine-associated paralytic poliomyelitis (VAPP) linked to the oral polio vaccine.
• A safer version of DTP called DTaP is licensed for use in 1997. Rather than using the whole pertussis bacterium, DTaP employs a subunit of pertussis called acellular pertussis.
• LYMErix, a Lyme disease vaccine, is licensed for use in 1998 (although it was discontinued in 2002 due to declining sales and fears about adverse side effects).
• Virus elimination: Measles is declared eliminated in the United States in 2000.

21st Century

Thus far, the 21st century has been marked by contrast insofar as vaccines are concerned. On the one hand, vaccine development has snowballed with an ever-widening range of vaccine platforms to build on. On the other, a rejection of vaccination by many in the general public has lead to the comeback of diseases once declared eliminated.

Among some of the achievements of the early part of the 21st century:

• FluMist, the intranasal flu vaccine, is approved in 2004. Unlike flu shots made with inactivated virus, FluMist involves a live, attenuated virus.
• Virus elimination: Endemic rubella is declared eliminated in the United States in 2004.
• The Tdap vaccine is approved for use in 2006. While it protects against the same diseases as DTaP, it is largely used as a booster to sustain immunity in older adults. The pneumococcal vaccine is another instance in which booster shots are recommended for adults 65 or over.
• Gardasil, the first vaccine to protect against human papillomavirus (HPV), is approved in 2006. This is followed by Cervarix (discontinued in 2016) and Gardasil-9 (an improved version that replaced the original Gardasil in 2017).
• In 2011, the influenza vaccine Fluzone High-Dose is approved for use in older adults who tend to have a less robust response to traditional flu shots and are more likely to experience severe complications of flu.
• Zostavax, a live-attenuated vaccine that protects against herpes zoster (shingles), is approved for use in 2011. It is considered the standard of preventive care until the release of a safer and more effective inactivated vaccine, called Shingrix, in 2017. (Zostavax was voluntarily discontinued by the manufacturer in November 2020 and is no longer available in the United States.)
• With the emergence of more virulent flu strains and the decline in vaccine efficacy rates, quadrivalent flu vaccines become the standard of preventive care in 2013.
• Trumenba, the first vaccine to protect against serogroup B meningococcal disease, is licensed for use in 2014. When used with vaccines that protect against serogroups A, C, W, and Y, Trumenba can prevent potentially life-threatening complications in high-risk groups—particularly during meningitis outbreaks at colleges and universities.
• Fluad is the first adjuvanted flu vaccine used solely in adults 65 and older. Approved for use in 2015, it doesn't contain more antigens like Flublock High-Dose. Rather, it involves a non-antigenic substance—called an adjuvant—that boosts the overall immune response to the flu vaccine.
• On December 11, 2020, the Pfizer/BioNTech COVID-19 vaccine is the first vaccine granted emergency use authorized (EUA) by the U.S. Food and Drug Administration (FDA) for the prevention of COVID-19. It is also the first vaccine successfully built on a messenger RNA (mRNA) platform.
• On December 11, 2020, the Moderna COVID-19 vaccine —also an mRNA vaccine—is the second vaccine to be granted EUA status.
• On February 27, 2021, the Janssen/Johnson & Johnson COVID-19 vaccine is granted EUA status. Unlike the other two vaccines, this is a recombinant vector vaccine that delivers a fragment of COVID-19 to cells via a weakened cold virus.
• On July 13, 2022, the Novavax COVID-19 Vaccine is granted EUA status. It is the first protein-based subunit vaccine for COVID-19 that has been approved in the United States. It is combined with an adjuvant to boost the immune response to the vaccine.

Despite the increasing safety and efficacy of vaccines, growing anti-vaccine sentiment in the United States has led to a decline in vaccination rates and the re-emergence of diseases once considered eliminated.

Public health officials fear that the same could occur with other diseases once thought eradicated.

A Word From Verywell

Vaccines work. Despite conspiracy theories and claims to the contrary, the benefits of recommended vaccines invariably outweigh the risks.

Consider that a disease like diphtheria killed over 15,000 children in the United States in 1921 but is rarely if ever seen today. (The last two cases were reported in 2004 and 2015.) Or that a disease like polio, which in 1916 caused over 2,000 deaths in New York City alone, has largely been consigned to the history books.

As the COVID-19 pandemic of 2020-2021 readily reminds us, vaccines not only protect individuals from severe illness and death, but they protect the population at large by preventing the spread of infection.

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