In 1918 an epidemic dubbed the Spanish flu killed at least 50 million people. What have we learned since then?

In the fall of 1918, near the end of World War I, another threat to human life was looming. While the danger had been growing since the previous year, the Spanish flu reached pandemic levels. The disease spread almost everywhere on Earth, including the Arctic. However, during the end of World War I the Spanish press were among the first to cover the event in detail. Even the Spanish king himself was afflicted, leading to the mistaken belief that the disease started in Spain.

A quarantine facility for infected soldiers. (Photo courtesy of CDC)

Once government officials acknowledged the danger, cities took extreme measures to attempt to stop the spread of the disease. Schools, theaters, and other public gathering places were forced to close, and the United States government earmarked an unprecedented sum to halt the spread. Vaccines were developed and promoted by governments, although we now know they were targeting the wrong influenza strain. In the end, it is estimated that between 50 and 100 million people died of the disease or from complications of the disease.

Although there were attempts at vaccination during the pandemic, the functional version of flu vaccines in the United States began in the 1940s. Thomas Francis Jr. and Jonas Salk, better known later for their work on the polio vaccine, were instrumental in the development of flu vaccines. The first approved version of the vaccine was administered to soldiers in 1945, during World War II. Civilians were able to get vaccinated the following year.

Influenza viruses are able to mutate through antigenic drift and shift, which necessitates constantly adapting vaccine varieties. Since adopting new standards in 1973, the World Health Organization (WHO) determines the three most likely influenza strains, or candidate vaccine viruses (CVVs), to include in that year’s flu shot. There are also quadrivalent vaccines on the market.

Volunteer drivers perform ambulance duty in St. Louis. (Photo Courtesy of CDC)

Until recently, almost all flu vaccines have been manufactured using fertilized chicken eggs to propagate the virus. This technique involves growing each of the three predicted CVVs in separate eggs, and combining the three into one vaccine. One of the primary advantages of this strategy is that eggs are cheaper and propagate influenza to high titers. There are drawbacks, though. In some rare instances, the egg-based vaccines have caused allergic reactions. If an avian influenza strain were to become virulent, it could decimate poultry populations and cause a shortage of eggs for consumption or vaccine manufacturing, which occurred in 2015 with the highly pathogenic H5N2. There are now viral vectored vaccines on the market now that can help the poultry producers if another H5 outbreak like this occurs. These vaccines use Charles River’s Specific Pathogen Free (SPF) cells or eggs.

Still, egg-based techniques can be time consuming and unpredictable, with a six month lag between CVV isolation and finished vaccines, and fluctuations in the amount of vaccine harvested from each egg. Therefore, influenza vaccine manufacturers are seeking alternatives.

Influenza virus.

Alternatively, researchers have been working on cell-based vaccines to replace the standard egg method. In 2016 the U.S. Food and Drug Administration (FDA) approved the manufacture of Novartis’ vaccine Flucelvax using cell-based virus isolation. In this process, cultured animal cells are used to incubate the viruses instead of eggs. This process not only eliminates the potential problem of an influenza outbreak, but also allows for faster manufacturing, though not necessarily faster than traditional methods where influenza in eggs incubates in 48-72 hours

Since the Spanish flu crisis there have been three more influenza pandemics, most recently in 2009. Luckily, since the invention of vaccines and other advances in modern health care, none have been nearly as deadly as the 1918 pandemic. However, without a universal flu vaccine, and with some people unable or unwilling to get a yearly shot, it is only a matter of time before another outbreak occurs. Influenza is a tricky virus, and has even made headlines this year with new strains being found in dogs. But with continually advancing technologies like cell-based vaccines, future doctors are ready to put up a fight against the flu.