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How are Vaccines Made?

U.S. Military and Vaccine History

Last update 17 January 2018

Military research programs throughout history have made significant contributions to medicine and, in particular, to vaccine development. These efforts have been driven primarily by the effects of infectious disease on military conflicts: smallpox devastated the Continental Army in 1776, as well as troops on both sides of the United States Civil War; typhoid fever was common among soldiers in the Spanish American War. More person-days were lost among U.S. soldiers in malaria-endemic regions to malaria than to bullets throughout the entire 20th century; indeed, malaria continues to sap military strength into the current century.

To respond to these diseases and the many others that threaten both soldiers and the public, military forces have devoted significant time and effort toward public health methods and medical research.



Smallpox was a scourge of the American Colonies, decimating Native American populations and then playing a part in the Revolutionary War. British soldiers had better immunity to the disease than the colonial troops, and may have even used it as a weapon. In 1776, half of the 10,000 Continental Army soldiers around Quebec fell ill with smallpox; of the outbreak, John Adams wrote, “The smallpox is ten times more terrible than the British, Canadians and Indians together. This was the cause of our precipitate retreat from Quebec.”

The following year, George Washington, as commander-in-chief of the Continental Army, ordered mandatory inoculation against smallpox for any soldier who had not gained prior immunity against the disease through infection.  The procedure in that era was known as variolation, intentionally exposing someone to a mild form of the smallpox virus (Jenner would not develop the smallpox vaccine until 1796). [.] For the British Army in the North American colonies, inoculation was voluntary.

As a result of Washington’s orders, the Continental Army was the first in the world with an organized program to prevent smallpox. Some historians have suggested that if smallpox inoculation had been performed earlier, the smallpox outbreak among Continental soldiers in Quebec could have been avoided—speeding up the conclusion of the Revolutionary War and potentially allowing for the addition of some or all of the British colony of Canada to the United States.

Yellow Fever

Yellow fever was a serious problem for U.S. troops during the Spanish-American War of 1898. In response, the Army created a Yellow Fever Commission, headed by physician Walter Reed. The Commission members traveled to Cuba and, after extensive experiments and observation, validated a theory presented by Cuban physician Carlos Finlay two decades earlier:  mosquitoes were responsible for the spread of the disease.  Later investigators showed that a virus was its actual underlying cause, transmitted from one person to another using mosquitoes as vectors.

Later, the Commission’s work would lead to yellow fever control programs for both military camps and Cuban cities and towns.  American physician William Crawford Gorgas organized these programs for both Cuba and the Panama Canal region. The control efforts by Gorgas’s group allowed for the completion of the Panama Canal by the Americans after French efforts were abandoned due to the difficulties of both yellow fever and malaria. After serving as Surgeon General of the U.S. Army, Gorgas would eventually join the Rockefeller Foundation’s Yellow Fever Commission as director of its work on yellow fever eradication. Years later, Harvard instructor Max Theiler would also join the commission and develop the 17D vaccine against yellow fever. Theiler, a virologist, would eventually win the Nobel Prize for his efforts, and the 17D vaccine is still used today.


After World War II, the majority of acute respiratory disease cases among U.S. military trainees were the result of adenovirus infections. Adenovirus infections can vary in symptoms from those similar to a common cold to pneumonia or bronchitis; at least 52 different types of adenoviruses can infect humans. In severe cases, trainees could die of respiratory distress induced by the adenovirus infection.

Maurice Hilleman, a microbiologist who would eventually be involved in the development of more than 40 vaccines, joined the U.S. Army Medical Center’s Department of Respiratory Diseases after leaving E.R. Squibb & Sons in 1948. That research center would soon be renamed the Walter Reed Army Institute of Research (WRAIR), and Hilleman was still working there in 1953, when he flew to Fort Leonard Wood, Missouri, to investigate a suspected influenza outbreak among Army troops.

Instead, when Hilleman and his group isolated viruses from the infected troops, they discovered that they had isolated not influenza virus, but multiple strains of a newly discovered type of virus—the group that would eventually be named adenoviruses.

Just three years later, in 1956, an adenovirus vaccine was created at WRAIR. It was an inactivated vaccine that protected against two forms of adenovirus infection, types 4 and 7, which accounted for the majority of acute respiratory diseases among trainees. (A separate vaccine developed at the National Institutes of Health protected against type 3 in addition to types 4 and 7.) Manufacturing problems led to the license for the vaccine being revoked in 1963, but two live-virus vaccines were developed just a few years later. These vaccines were unique in being produced as oral tablets with a coating that resisted stomach acid.

After extensive military studies, both vaccines were given to new military trainees “within hours after their arrival” at basic training beginning in 1971. In 1994, however, the vaccine’s manufacturer ended production of it, and all stocks were depleted in 1999. Outbreaks of acute respiratory disease caused by adenoviruses rose among military trainees following discontinuation of the vaccination program. In 2001, the Army provided funds to re-establish an adenovirus vaccine, and the government contracted with a manufacturer to restore a production line for adenovirus type 4 and type 7 vaccine tablets. The vaccine was licensed in March 2011, and the U.S. military deployed it to training facilities beginning in October 2011. Surveillance of adenovirus illness since then shows a marked decrease in incidence of all serotypes of adenovirus after re-introduction of the vaccine.

HIV and Malaria Vaccine Research

Today, military researchers are heavily involved in efforts to develop treatments and vaccines for malaria and HIV infection. The U.S. military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research studies not only care and treatment but HIV prevention as well. MHRP scientists, collaborating with the U.S. National Institutes of Allergy and Infectious Diseases (NIAID), developed a viral vector HIV vaccine candidate that has reached human clinical testing in combination with another vaccine product. Separately, U.S. military researchers have also contributing to the testing of the leading vaccine candidate for malaria. Developed in cooperation with GlaxoSmithKline, the RTS,S malaria vaccine candidate was tested in Phase 3 clinical trials and was found to be moderately effectively at preventing severe disease in children.



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