Fighting the flu: 18 pivotal moments in history that have brought us closer to a cure

Fifteen years before the deadly 1918 flu pandemic swept the world, Johnson & Johnson recognized that injectable medications and vaccines would become a crucial tool for rapidly delivering treatments into the bloodstream and began selling hypodermic needles that fit a standard syringe (shown at right).

This was forward-thinking for the time, since most drugs were ingested rather than injected, and injections were an advance over earlier vaccination methods. These tools would soon become critical instruments enabling doctors to administer the influenza vaccine.

This flu pandemic was the deadliest in modern history, infecting an estimated 500 million people worldwide and killing up to 50 million—an even more devastating death toll than World War I. More than 25% of the U.S. population became sick.

Johnson & Johnson played a key role in helping to prevent the spread of the virus by introducing the epidemic mask, made from sterile gauze. It proved so effective that it was also used in later outbreaks.

Influenza vaccine development—a high priority for the U.S. military following the deaths of approximately one in every 67 soldiers from the flu during the 1918-1919 pandemic—took a major step forward when researchers at the UK’s Medical Research Council were able to isolate the virus (shown at right) from humans.

Virologist Patrick Laidlaw and his team were working with ferrets to develop a distemper vaccine when the animals caught the flu from Wilson Smith, one of the scientists in the laboratory. The team dubbed it the “W.S.” virus, and their discovery made it possible to develop a vaccine.

Soviet scientist A.A. Smorodintseff made the first attempt to vaccinate people with a live influenza vaccine. Following in the footsteps of Louis Pasteur—who had made the first known attempt to vaccinate humans with a live, attenuated viral strain of rabies in 1885—Smorodintseff passed the live flu virus about 30 times in eggs, so it lost its virulence. He reported that those injected with the modified virus developed a slight fever but were protected against reinfection.

The attenuated virus was then used for mass production of a vaccine that was largely administered to factory workers, who were susceptible to outbreaks due to close working conditions.

This whole-virus, inactivated influenza A and B vaccine was first tested in military recruits and college students before it received approval for military use in the United States. A year later, it was approved for civilian use, as well. At right, schoolchildren wait in line for immunization shots at a child health station in New York City, circa 1946.

There are four types of influenza virus—A, B, C and D—but only the A and B types are thought to cause viral epidemics in humans, according to the CDC.

Disposable syringes and needles were introduced in the 1950s, and were mass-produced starting in 1954.

JELCO®, then part of the Johnson & Johnson family of companies, introduced a new line of one-time use hypodermic needles and syringes in 1964 that helped prevent cross-contamination between patients during the administration of injected medicines and vaccines, such as the influenza vaccine.

This was the second major influenza pandemic of the 20th century, killing about 2 million worldwide, including almost 70,000 in the United States. It was caused by a virus known as influenza A subtype H2N2 (shown at right), a mixed strain many scientists believe originated from a combination of bird (the Spanish flu pandemic was caused by a virus that developed from an avian source) and human flu viruses.

Influenza strains are characterized by two proteins on the outer surface of the virus: hemagglutinin and neuraminidase (represented by H and N, respectively). There are 14 versions of the H protein and nine versions of the N protein, according to the American Council on Science and Health.

The virus was first identified in Guizhou, China, in 1956. It spread to Singapore by February 1957, Hong Kong by that April and the U.S. by June. A vaccine was developed to contain the outbreak in 1957, but the strain would later evolve via antigenic shift into H3N2, causing a milder pandemic between 1968 and 1969.

The third major flu pandemic of the century, the Hong Kong pandemic (the first known outbreak of the H3N2 strain), killed about 1 million people worldwide, accounting for 34,000 deaths in the United States.

Compared to the first two pandemics of the century, this one yielded a lower death rate, with a case-to-fatality ratio below 0.5%.

Possible reasons for this include the fact that there was some immunity against the N2 virus amongst those who had survived the Asian flu pandemic; the outbreak struck around the winter school holidays, limiting its spread in schools; improved medical care better supported the very ill; and antibiotics were available to help ward off secondary bacterial infections.

Technically considered the fourth pandemic of the 20th century (there is no accurate death count on record), this outbreak—which started in China and Russia but eventually spread worldwide—mainly affected people under the age of 25.

Researchers would later theorize that an older H1N1 virus had mysteriously resurfaced, only impacting younger people who had never been exposed to it.

The first trivalent (three-component), egg-cultured flu vaccine was created, containing two influenza A strains (H1N1 and H3N2) and one influenza B strain, which were the most common strains in circulation at the time.

This was the first time a single vaccine was able to protect against three different strains of the flu, and this type of vaccine is still given today.

Currently, the World Health Organization recommends the composition of influenza vaccines each year, based on the results of its global influenza surveillance, which helps the organization predict the strains most likely to circulate in the coming flu season.

Two antivirals, oseltamivir phosphate and zanamivir, were approved by the Food and Drug Administration (FDA) for the treatment of influenza A and B. Both medications were shown to reduce such flu symptoms as fever, chills, muscle aches, sore throat and a runny or stuffy nose.

Prior to their approval, people suffering from the flu had to rely on over-the-counter drugs to help relieve their symptoms. Both of these medications require a physician’s prescription and are effective in patients who’ve been symptomatic for no more than 48 hours.

The first nasally administered influenza vaccine was licensed for healthy, nonpregnant people between the ages of 5 and 49. In 2007, it was also approved for younger kids between the ages of 2 and 5. This type of vaccine is helpful for those who are unwilling or unable to receive the vaccine via injection.

The FDA approved the first U.S. vaccine for humans against the avian influenza virus H5N1. Although human cases of avian influenza occur only occasionally, the mortality rate when people do become infected is about 60%, according to a study published in Pathogens and Global Health.

Johnson & Johnson announced that it will begin work on the development of a new universal flu vaccine designed to fight all types of the virus, using molecules called mini-HA antigens that contain parts of the flu virus that appear within a wide variety of viruses. The goal: provide longer-lasting protection than the regular seasonal flu shot.

The catalyst for this was a 2008 discovery by Crucell (now part of the Johnson & Johnson family of companies) that human antibody CR6261 could protect against a broad spectrum of influenza viruses. It was then that researchers realized humans are capable of producing antibodies against the part of the influenza virus that doesn’t change—an idea that was not accepted before this time.

“Current flu vaccines have to be changed year to year, and even then, they only reduce the risk of developing the flu by 40 to 60%,” explains Ted Kwaks, Ph.D., Director for Project Management and External Innovation, Viral Vaccines Discovery, Janssen Pharmaceuticals, part of the Johnson & Johnson family of companies. “The theory is that, ultimately, we’ll put these antigens into a vaccine that will provide protection against virtually all flu strains.”

The H1N1 (swine flu) pandemic—caused by the same strain of virus responsible for the 1918 pandemic—originated in Mexico and spread rapidly, killing up to a half-million people worldwide. There were about 60 million reported cases of infection, with more than 274,000 hospitalizations and upward of 12,000 deaths in the United States.

The virus isolated from patients in the U.S. was made up of genetic elements from four different flu viruses: North American swine influenza, North American avian influenza, human influenza and a swine influenza virus typically found in Asia and Europe. One characteristic of the swine flu was that it did not disproportionately affect those over the age of 60, like most other strains, since those who contracted the flu before 1957 seemed to have some immunity to H1N1.

Although the flu is viral, the H1N1 strain damaged the lungs of its victims, leaving them susceptible to such secondary bacterial infections as pneumonia. Thankfully, antibiotics were readily available in 2009, which greatly reduced these complications.

The first quadrivalent vaccine, which fights against four strains of the flu—two influenza A and two influenza B lineage strains—was approved by the FDA.

The addition of a second influenza B strain to the vaccine aimed to provide broader protection against circulating flu viruses. Although influenza B viruses have never been reported to be responsible for a pandemic, they have been reported to cause localized epidemics, and they have been the most prevalent viruses during certain flu seasons.

The FDA approved the antiviral peramivir for the relief of flu symptoms, including cough, sore throat, nasal congestion, headache, feverishness, muscle aches and fatigue.

Unlike other drugs of its kind, it’s taken intravenously and only requires one dose. The medication is available to patients admitted to the Emergency Department who may not be candidates for oral treatment, including those who are severely dehydrated, have swallowing issues or who do not have a fully functioning gastrointestinal tract.

Johnson & Johnson announced a collaboration with the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response to develop a comprehensive portfolio of therapeutics and vaccines to protect communities in the event of an influenza pandemic. The hope is to help prevent the more than 1 billion cases of influenza globally each year that result in 5 million cases of severe illness and up to a half-million deaths.