University of Sourthern California


Important Vaccines in History

Disease has ravaged humankind for its entire existence. Pandemics took hold once people began living in close quarters. Ideas of immunization date back to 1,000 CE in China, but the methods were crude. Then, in the late 18th century, Dr. Edward Jenner took a bold leap in vaccine development when he inoculated a boy with cowpox to make him immune to smallpox. Since then, a number of vaccines have ended endemics and pandemics and protected people around the globe from infections ranging from influenza to COVID-19.

To learn more, check out the infographic below, created by USC’s Master of Public Health program.

The Importance of Vaccines

A vaccine is any combination of weakened or dead germs, or parts of germs, that can be injected into the body to trigger an immune response. Vaccines are an important tool in the public health arsenal to stop the spread of disease.

The Damage of Diseases

Endemic, epidemic and pandemic diseases caused global devastation before vaccines stopped or slowed them.

For example, smallpox killed 30% of those who contracted it. It also destroyed the Aztec empire and wiped out 90% to 95% of the Indigenous population after European explorers brought it to the Americas, possibly leading to global cooling.

Tetanus has a 20% fatality rate and requires months of recuperation. It kills as many as 293,000 globally each year and is responsible for 7% of neonatal and 5% of maternal deaths annually.

Polio kills up to 5% of children who contract it and up to 30% of adults. It paralyzed up to 20,000 Americans annually in the early 1950s and added a $1.5 billion burden to the global economy annually at the height of its prevalence.

The flu kills an average of 389,000 people worldwide and costs the U.S. economy $5.8 billion annually. During the 1918 flu pandemic, it caused a 6% decline in global GDP and an 8% drop in consumption.

COVID-19 killed more than 4 million globally from late 2019 through mid-2021, plunged the global economy into the worst recession since World War II, caused a 3.5% drop in global economic growth and led to $16 trillion in government financial support.

Beyond Health

Vaccine efforts around the globe have led to improved overall health systems, the passage of laws to regulate and control the supply of medications, and the establishment of state and local health departments.

Benefits of Vaccine Dissemination and Development Efforts

The National Institutes of Health started overseeing vaccine manufacturers in 1902. Government efforts to protect citizens from adulterated vaccines and drugs began with the passage of the Biologics Control Act in 1902. Later, the Polio Vaccination Assistance Act established federal participation in and funding of immunization efforts.

Vaccination efforts are important around the world. Global polio eradication efforts increased overall childhood vaccine access by 75%. Vaccination programs provide significant economic benefits to developed and developing nations alike. For example, ending smallpox in the U.S. cost more than $100 million but saved $1.35 billion annually. Work on one vaccine, or type of vaccine, allows the global community to be ready for unknown disease threats that may emerge, as with COVID-19.

Types of Vaccines

Modern vaccines mimic infection so the immune system’s natural response kicks in. The body remembers how to fight the infection if the germs later enter the body. Vaccine development depends on the pathogen (virus or bacteria), the disease process and the immune system response.


Live-attenuated vaccines use living but weakened germs. They’re the best way to condition the immune system but can’t be given to those with compromised immune systems. Use cases for these types of vaccines include viruses and bacteria. Measles, mumps, rubella, smallpox and chickenpox are examples of live-attenuated vaccines.


Inactivated vaccines use dead germs, so they can’t make people sick, but they also produce a weaker immune response, necessitating multiple doses. Use cases are viruses and bacteria. Polio, influenza, rabies and hepatitis A are examples of inactivated vaccines.


Toxoid vaccines use weakened toxins called toxoids. These vaccines are used to protect against toxin-producing bacteria such as diphtheria and tetanus.


Subunit vaccines use a part, or subunit, of the pathogen, producing a mild immune response while still teaching the system to recognize the threat. This category also includes conjugate, recombinant and polysaccharide vaccines. Subunit vaccines are used against viruses and bacteria. Examples include pertussis (whooping cough), shingles, tetanus, pneumococcal disease and hepatitis B.


Messenger RNA vaccines use messenger ribonucleic acid (mRNA) to teach the immune system to make part of the disease protein, triggering an immune response that creates antibodies. These are used against viruses. The only approved mRNA vaccine is the one against COVID-19. It’s also been studied and used provisionally against influenza, Zika and rabies.

Viral Vector

Viral vector vaccines use a different, harmless virus called a vector to penetrate cells and deliver instructions for making antigens of the target virus, which triggers an immune response. They are used against viruses and are approved to fight Ebola and COVID-19.


DNA vaccines use a particle of the virus’s genetic code encased in a small bit of DNA called a plasmid to instruct human cells to produce the virus and generate an immune response. This is next-gen vaccine technology, so there are no commercial products yet.

10 Key Vaccines in History

As far back as 400 BCE, Hippocrates wrote about epidemics caused by diseases such as mumps and diphtheria. Variolation, where individuals were deliberately exposed to small doses of disease materials through inhalation or skin pricks, occurred in Asia and Africa in the 1100s, leading to Dr. Jenner’s smallpox experiment. But in the late 1880s, a host of scientists made great leaps in understanding germs, identifying specific disease-causing organisms and laying the foundation for vaccine development. Here are the timelines of key development stages for 10 key vaccines.


Building on variolation, live cowpox was injected into a boy in 1796, followed by live smallpox days later. Two years later, the full vaccine was developed. In 1949, the U.S. saw its last case of the disease, and in 1980, the WHO declared it eradicated.

Diphtheria, Tetanus and Pertussis (DTP)

From the late 1800s to the early 1900s, the bacteria, toxins and disease process was discovered. Then, vaccine development took off with a diphtheria antiserum in 1901, tetanus antiserum in 1914 and a pertussis vaccine in 1915. It was the first vaccine to use inactivated cells. In 1949, the three vaccines were combined into one shot, labeled DTP.


Three types of poliovirus were identified in 1931. In 1954, the first poliovirus was grown in a lab, and the following year, production of an inactivated vaccine began in the U.S. An oral vaccine was licensed in 1961, and the next year, the Polio Vaccination Assistance Act became the first federal involvement in vaccine efforts via funding to states for inoculation programs.

Measles, Mumps and Rubella (MMR)

In 1945 and 1954, mumps and measles viruses were isolated, respectively. A live-attenuated measles vaccine was licensed in 1963. The following year, a rubella epidemic infected 12.5 million people and killed thousands. In 1966, the measles eradication program launched, dropping cases 90% in two years. The next year, a mumps vaccine was licensed. In 1969, the rubella virus was isolated, and in 1971, the first combined MMR vaccine was licensed. It became MMRV in 2005 when varicella (chickenpox) was added.


The worst flu pandemic of modern times began in 1918, infecting 500 million people worldwide and killing 50 million. In 1931, the swine flu virus was identified, followed two years later by human influenza. The first flu vaccine was administered to U.S. troops in 1942; it was made available to the public in 1945. The haemophilus influenzae type b (Hib) polysaccharide vaccine was licensed in 1985, and a subunit (conjugate) Hib vaccine was licensed two years later. In 1996, a combined vaccine against Hib and hepatitis B was approved. In 2012, several vaccines were approved: the first seasonal flu shot, a new Hib vaccine and a vaccine against meningococcal disease.


After the first cases of what came to be known as COVID-19 appeared in late 2019, Chinese scientists released the gene sequence of SARS-CoV-2, the virus that causes COVID-19, in 2020. Due to prior work that had been done on mRNA and viral vector vaccine technology, vaccine development proceeded with unprecedented speed. In 2020, the first mRNA vaccine was approved for COVID-19 in the U.K., followed by emergency-use authorization for two mRNA vaccines in the U.S. the same year. In 2021, a viral vector vaccine was given emergency-use authorization for COVID-19.

Improving Health for Global Benefit

Improved health, better global health equity, and the establishment of standards in health care and medicine are just some of the benefits of vaccine development and vaccination programs. Vaccines have done great good for humanity, and that good continues to this day and into the future.


Biotech Primer Weekly, “DNA Vaccines Explained”

The Brookings Institution, “Social and Economic Impact of COVID-19”

Centers for Disease Control and Prevention, 14 Diseases You Almost Forgot About

Centers for Disease Control and Prevention, Understanding How Vaccines Work

Centers for Disease Control and Prevention, Vaccines for Your Children: Measles

Centers for Disease Control and Prevention, Vaccines for Your Children: Mumps

Children’s Hospital of Philadelphia, Vaccine History: Developments by Year

European Centre for Disease Prevention and Control, Disease Factsheet About Tetanus

The Food and Drug Administration, FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine

Frontiers in Microbiology, “Impact of Vaccines; Health, Economic and Social Perspectives”

Frontiers in Public Health, “Vaccines Through Centuries: Major Cornerstones of Global Health”

Gavi, “What Are Viral Vector-Based Vaccines and How Could They Be Used Against COVID-19?”

Harvard Health Blog, “Why Are mRNA Vaccines So Exciting?”

History, “How 5 of History’s Worst Pandemics Finally Ended”

History, “Pandemics That Changed History”

History, “The Spanish Flu: Fighting the Spanish Flu”

Immunization Action Committee, “Polio: Questions and Answers”

Immunization Action Committee, Vaccine Timeline

Journal of Global Health, “Global Mortality Associated With Seasonal Influenza Epidemics: New Burden Estimates and Predictors From the GLaMOR Project”

Merriam-Webster, Definition of Vaccine

National Bureau of Economic Research, “The Coronavirus and the Great Influenza Pandemic: Lessons From the ‘Spanish Flu’ for the Coronavirus’s Potential Effects on Mortality and Economic Activity”

The New York Times, “Ebola Vaccine, Ready for Test, Sat on the Shelf”

Proceedings of the National Academy of Sciences, “Future Epidemiological and Economic Impacts of Universal Influenza Vaccines”

Science, “Chinese Researchers Reveal Draft Genome of Virus Implicated in Wuhan Pneumonia Outbreak”

U.S. National Library of Medicine, “Smallpox: A Great and Terrible Scourge, Variolation”

World Health Organization Global Polio Eradication Initiative, History of Polio

World Health Organization, Coronavirus (COVID-19) Dashboard

World Health Organization, Smallpox