By Barry C. Fox, M.D., University of Wisconsin
For human vaccines to be accessible on a universal scale, complex production methods, thorough quality supervision, and valid distribution channels are required to verify the efficacy of the product for the end user. Various vaccine production methods are used, such as ‘live’ or ‘killed’ vaccines, depending on the pathogen type and the body’s response.

Rubella Virus and Vaccine Development
One boost for the vaccine movement occurred in 1941 when the rubella virus was found to cause fetal abnormalities in pregnant women. An Australian ophthalmologist noted that pregnant women who contracted rubella transmitted cataract eye disease to their fetuses.
Four groups of scientists managed to attenuate the live rubella virus, three from primary animal cells and one from human cells. The rubella vaccine was the first vaccine created with the use of human cell lines by virologist Stanley Plotkin.
Plotkin grew the virus through cell lines 25 times at lower-than normal-body temperatures (86 degrees F) in order to weaken the virus so it would no longer be infectious, but would be strong enough to provoke an immune response.
Interestingly, the three animal cell vaccines were approved in 1970 in the United States, and the human vaccine was only approved in Europe. Evidently, there was a bias against using human cells for fear of contamination. But eventually, the human vaccine not only replaced the animal cell line vaccines but Plotkin’s vaccine is still used today in the MMR vaccine given to children today.
This is a transcript from the video series An Introduction to Infectious Diseases. Watch it now, on Wondrium.
Different Ways Vaccines Can Be Made
Vaccines can be made in several different ways. First, using live viruses, but weak enough not to cause disease—as with rubella. Secondly, using inactivated/killed bacteria or viruses, such as polio vaccines in the United States and most influenza vaccines.

Third, using inactivated toxins known as toxoids of bacterial germs, such as diphtheria and tetanus. And fourth, using a portion of the germ coating, for example, the sugar coating of pneumococcus.
But why is there a need to use four different types of vaccines?
Well, it’s because different micro-organisms have more ideal targets to maximize the body’s immune response. For example, although scientists have been working on an HIV vaccine for more than a decade, the ideal target for vaccination has yet to be identified.
Learn more about malaria and tuberculosis.
Vaccine Production Methods

The live attenuated vaccine (like for the rubella virus) is too weak to cause significant illness but strong enough to provoke an immune response that protects against future infection. Inactivated or killed vaccines are made by deactivating a pathogen, typically using heat or chemicals such as formaldehyde.
This destroys the pathogen’s ability to replicate but keeps it intact so it can still be recognized. This type of vaccine is most likely to require a booster because it does not duplicate the normal infectious process in humans.
Toxoids are different because the illnesses they induce are not from bacteria themselves but from toxins produced by bacteria. Immunizations can be made by inactivating the toxin using chemicals or heat.
Both subunit and conjugate vaccines contain only pieces of the pathogens they protect against. Conjugate vaccines, however, are made utilizing pieces from the outer coating of bacteria chemically linked to a carrier protein, and then the combination is used as a vaccine. The carrier protein is often chosen to maximize the human immune response to the entire complex, not just the bacterial coating.
Learn more about milestones in infectious disease history.
Disease Outbreaks and Vaccination Throughout History
In Stockholm, in the 1860s, smallpox outbreaks had been contained, so the population became lackadaisical about being vaccinated. In 1872, a majority of the population refused smallpox vaccination, and the vaccination rates fell to below 40 percent. A major smallpox epidemic occurred just two years later.
A more recent example took place in the 1990s when more than 150,000 Russians contracted diphtheria resulting in more than 6,000 deaths. In early 2014, there were measles outbreaks in five states. In California alone, there were 49 confirmed cases.
In one instance, an unvaccinated boy who was traveling in Europe with his family contracted measles. Upon his return, he unknowingly exposed over 800 people (including 11 unvaccinated children and 3 toddlers).
This, of course, is not an isolated incident. Global travel presents serious infection risks from diseases that have not been contained elsewhere. In 2011, California had more than 2,000 whooping cough cases and 10 infant deaths. Only one of the 10 infants had received a first dose of the vaccine.
Learn more about emerging and reemerging diseases.
The Anti-vaccination Movement
Back in the mid-1800s, vaccines were deemed compulsory in Britain. There were severe punishments for not being vaccinated, including fines and imprisonment. They recognized everyone’s health was interconnected.
Some people had strong feelings about this and said this was a violation of their civil liberty, hence, the anti-vaccination movement. Fifty years later, the law was amended to allow for conscientious objectors.
There has been much chatter in the press about the recent anti-vaccination movement. They claim, “I had chickenpox, measles, and mumps as a kid, and I came through it just fine.”
Everybody knows that natural infections can have a negative influence on childhood development, and can cause complications or even death. For example, about one in four young children with whooping cough develop complications like pneumonia or even stop breathing.
Children with chickenpox can develop a brain infection called encephalitis, and others have developed deadly toxic shock syndrome from their hundreds of pox wounds and bacterial superinfections compared to none from the vaccine.
Common Questions about Vaccine Production, Disease Outbreaks, and the Anti-vaccination Movement
There are four main vaccine production methods. First, using live viruses, but weak enough not to cause disease. Secondly, using inactivated/killed bacteria or viruses. Third, using inactivated toxins known as toxoids of bacterial germs, and fourth, using a portion of the germ coating.
Most influenza vaccines use inactivated/killed bacteria or viruses, as do polio vaccines in the United States.
There are several vaccine production methods because different microorganisms have more ideal targets to maximize the body’s immune response.