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Immunology 101 Series: 5 Ways Vaccines are Made

By Aimee Pugh-Bernard, PhD

As you know from reading the first Immunology 101 Series post, vaccines are composed of non-disease causing forms of pathogen (the scientific term for ‘germs’ such as bacteria and viruses) that allow our immune system to create long-lived memory cells. Memory cells remember the pathogen from the first encounter with the vaccine and quickly defeat the real, disease-causing pathogen when it enters our body. Essentially, vaccines train our immune system to recognize and respond quickly to infection to keep us healthy!

While getting your flu shot this season, you may have been offered the choice of different types of vaccines. Live, attenuated? Inactivated? What do these terms mean, and how do they affect protection? Read on to find out!

Vaccines are made in several ways to create the most effective vaccine possible. Each pathogen is unique. Scientists use this information — the unique properties of each pathogen — to design the most effective vaccine using the same components found in the natural pathogen to stimulate an immune response.

The different types of vaccines and ways of creating them include live, attenuated, inactivated, subunit, conjugate, and toxoid. 

Live, attenuated
The term live, attenuated refers to a vaccine that uses a virus that has been weakened to the point that it is incapable of causing disease. This type of vaccine is highly effective as it most closely resembles a natural infection and produces a vigorous immune response. This means that both B cells and T cells, the major white cells of the immune system military, are called into action and will produce memory cells. These memory cells continually patrol our body,  ready to fight once we encounter the real, live pathogen through natural infection.

One limitation is that live, attenuated vaccines can’t be given to everyone. Children with a weakened immune system (as a result of an immunodeficiency or the use of chemotherapeutics to treat cancer) cannot receive live vaccines. Because their immune system is immunocompromised, or not fully functioning, exposure to a live virus, even one that has been weakened, is not recommended.

Examples of live, attenuated vaccines are the varicella ‘chickenpox’ vaccine, the MMR (measles, mumps, and rubella) vaccine, and the nasal spray form of the influenza ‘flu’ vaccine.

Inactivated vaccines contain a virus that has been killed and is completely incapable of causing disease. Even though the virus is not living, the cells of the immune system still respond to the killed virus in the vaccine and create memory cells in preparation for the real pathogen. An advantage to this approach is that children with weakened immune systems can receive inactivated vaccines because they do not cause even mild forms of the disease. A limitation is that inactivated vaccines sometimes require several doses – referred to as ‘booster doses’ — to achieve high levels of immunity.

Examples of inactivated vaccines are the injected or shot form of the influenza ‘flu’ vaccine, the inactivated polio vaccine, the hepatitis A vaccine, and the rabies vaccine.

Subunit vaccines contain pieces of the virus to create the vaccine. Rather than giving a whole pathogen, purified fragments of the pathogen can be used to trigger specific immune responses. In this type of vaccine the outer surface antigens (which can be thought of as the coat that surrounds the virus) are used to create subunit vaccines. This outer ‘coat’ is the portion of the pathogen the immune cells would encounter during a natural infection. Because subunits or pieces of pathogen are administered these types of vaccines are typically not as immunogenic, that is, they do not create as vigorous an immune response as whole pathogens and booster doses are often needed to be completely effective.

Examples of subunit vaccines are the Hepatitis B (HBV) vaccine and the human papillomavirus (HPV) vaccine.

Conjugate vaccines were created to combat bacterial pathogens that have an outer coating composed of sugar-like substances. The immune system, specifically the T cells, have difficulty responding to these types of bacteria; the sugar-like substances on the outer surface of the bacteria act as a sort of disguise that allow them to be almost invisible to the T cells of the immune system (if you are a Harry Potter fan you can compare these sugar-like substances to the cloak of invisibility). In order to make these sugar-like substances visible to the T cells within the immune system they are conjugated, or actually connected, to substances that these immune system cells can recognize and respond to, such as large, harmless proteins. The connection or conjugation of pieces of the outer coating sugar-like substances of bacteria to harmless proteins allows the immune system to respond. This is particularly helpful to infants that have immature immune systems that are not yet fully developed.

An example of a conjugate vaccine is the Hib vaccine that combats Haemophilus influenzae type b bacterium that infects the lining of the brain resulting in meningitis.

Toxoid vaccines contain inactivated or killed toxins called toxoids that are no longer capable of causing harm or disease. Toxins are poisonous substances produced by many types of bacteria. As a result, several bacteria cause disease through the production of harmful toxins.  Toxoid vaccines use inactivated toxins to allow for the production of an immune response but to eliminate the possibility of disease. Toxoid vaccines primarily induce B cells to produce antitoxin antibodies. Research has shown that antitoxin antibody levels decline slowly over time so booster doses are recommended every 10 years to maintain protection.

Examples of  toxoid vaccines are DTaP (pediatric form of the vaccine) and Tdap (adolescent and adult form of the vaccine) – the vaccines that are made to train the immune system against diptheria, tetanus, and pertussis (whooping cough).Quick Review 2

While there are several types of vaccines, all vaccines are created using a similar strategy: the pathogen is weakened to allow you to develop an immune response without becoming sick.

Vaccines are a safe and effective way to stop the spread of disease by building the immune system. Stay tuned for the next Immunology 101 Series post to learn how vaccines are made, tested and licensed for public use to ensure that we get the best and safest protection possible.

Check out these fun tools to better understand how vaccines are made:

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