In our vaccines 101 blog, we explain the basics of how they work, define the different types and explain the pros and cons of each technology as a disease-prevention tool.
How Do Vaccines Generally Work?
According to an October 2020 publication in Nature Reviews Immunology, leading authors Dr. Zhou Xing and Dr. Brian Lichty describe vaccines as requiring two components:
Proteins from the target virus (e.g., proteins from current coronavirus), and
An infection signal to alert the human’s immune system to the presence of a foreign invader.
In broad terms, vaccines work by stimulating a person’s immune system to “remember” certain protein patterns of a given virus, thereby enabling that person to launch an immediate immune response against that virus if it enters their body.
To learn more about the vaccines currently in clinical trials for COVID-19, read our Vaccines for COVID-19 blog.
What Are The Different Types of Vaccines?
There are several ways researchers classify vaccine types. At Amory Medical, we have separated them into three overarching categories with seven distinct subtypes (Fig 1):
1. Whole virus vaccines
Live attenuated virus
Inactivated or killed virus
Recombinant viral-vectored
2. Subunit-based vaccines
Protein subunit vaccines
Virus-like particles (VLPs)
3. Nucleic acid-based vaccines
mRNA vaccines
DNA vaccines
Whole Virus Vaccines
Whole virus vaccines use the entire disease-causing pathogen instead of a specific component from the virus. Differing methods of presenting the whole virus in a way that does not cause human disease are discussed in the three subtypes below.
Live-Attenuated Virus
One of the simpler ways of designing vaccines is to modify the infectious agent (virus or bacteria) such that it becomes harmless or less contagious, yet still “alive.” This modified infectious agent, often termed a live-attenuated virus, retains the key protein “patterns” as well as an infection signal while omitting the genes required to cause human disease.
The biggest advantage of these live-attenuated viral vaccines is that they often provide “one-shot” immunity, meaning that a single vaccination is sufficient to provide protection against the given virus. However, live-attenuated viral vaccines cannot be used in individuals with weakened immune systems because of their extremely rare ability to recreate a disease-causing virus in humans.
Inactivated Virus
Inactivated viral vaccines consist of a killed version of the infectious agent of interest and an adjuvant, or a substance that enhances the immune response to the killed virus. Inactivated viruses differ from live-attenuated viruses in that they consist of a killed version of the infectious agent whereas live-attenuated viruses are weakened, but not killed.
Because inactivated viruses generally produce weaker immune responses than live viruses, special chemicals termed adjuvants are required to ramp up the host’s response. Since the immune response is weaker, protection is temporary, therefore requiring repeated vaccination in order to be effective. Importantly, inactivated viral vaccines can be easily mass produced and are safe to use in immunocompromised individuals (i.e., individuals with decreased immune defenses).
Recombinant-viral vectored
Recombinant-viral vectored vaccines work by using an innocuous virus to carry protein “patterns” from the disease-causing virus. Upon vaccination, the “carrier” virus enters human cells and directs the cell to produce the protein “patterns” from the disease-causing virus. The immune system then generates a response against these protein “patterns” and not against the carrier virus. The most beneficial aspect of recombinant-viral vectored vaccines is they can provide “one-shot” immunity and have well-established safety profiles. However, they tend to have high production costs compared to other routes of vaccination.
Subunit-Based Vaccines
Unlike whole-virus vaccines, subunit-based vaccines only include specific pieces from the virus that best stimulate an immune response.
Protein Subunit
Instead of providing a weakened or killed version of the entire infectious virus, protein subunit vaccines only provide the protein “patterns” that elicit the strongest immune response. Although this platform can simplify vaccine development and production, it frequently mandates the inclusion of adjuvants to trigger a strong immune response. Because of the requirement for adjuvants, protein subunit vaccines often require repeated administration. Similar to inactivated vaccines, protein subunit vaccines are safe to use in immunocompromised patients.
Virus-Like Particles (VLPs)
Virus-like particles (VLPs) are a unique type of vaccine where multiple protein “patterns” from the virus are mixed together and spontaneously form a particle that structurally resembles the original virus. The main difference between VLPs and the virus itself is that VLPs lack the genetic material required to make any virus infectious. Although VLPs can induce immune responses in the body, they typically require adjuvants to enhance the response. Therefore, VLPs usually require repeated vaccination. Despite this, the safety of VLPs have been demonstrated and are amenable to large-scale manufacturing.
Nucleic Acid-Based Vaccines (mRNA, DNA)
Nucleic acid-based vaccines are similar to protein subunit vaccines, but instead of delivering protein “patterns”, they deliver the instructions for producing these proteins in the form of DNA or messenger RNA (mRNA).
In biology, proteins are built according to instructions present in the genetic code of DNA and mRNA (Fig 2). Another way of putting this is that DNA is converted to mRNA which is then used to generate mature proteins. Therefore, one way of providing protein “patterns” to cells is by delivering the instructions to create these proteins. This is the exact process that occurs with the DNA and mRNA nucleic acid-based vaccines.
Unlike protein-subunit vaccines, nucleic acid-based vaccines are thought to stimulate stronger immune responses, are easier to design, and likely have a simpler manufacturing process. These key advantages differ slightly between mRNA and DNA vaccines.
mRNA Vaccines
This innovative platform works by delivering the mRNA encoding the protein “pattern” from the infectious agent (e.g., coronavirus) to humans. Human cells take up this mRNA and convert it into mature protein that is structurally identical to the one expressed on the viral surface. Immune responses are then generated against this protein, thereby providing protection against the virus.
Importantly, because the mRNA solely encodes the protein “pattern” that elicits an immune response and omits the proteins required to make a contagious virus, mRNA vaccines are safe and non-infectious. Additionally, mRNA vaccines can be rapidly scaled-up for relatively inexpensive production. However, similar to other subunit-based vaccines, the mRNA platform requires use of adjuvant to trigger a strong immune response, therefore requiring repeated vaccination. Since mRNA vaccines are chemically unstable, they require refrigeration and sometimes freezing to maintain efficacy, thereby limiting widespread use.
DNA Vaccines
This vaccine methodology functions by delivering DNA encoding the protein “pattern” from the infectious agent (e.g., coronavirus) to humans. Unlike mRNA vaccines, DNA vaccines rely on human cells to convert the DNA to mRNA and then produce protein from the mRNA (Fig 2). In other words, DNA vaccines require an extra step in generating the protein “pattern” that elicits the immune response.
Functionally, this can result in decreased potency of the immune response relative to mRNA vaccines. However, unlike mRNA vaccines, DNA vaccines are stable at higher temperatures and do not require refrigeration. Therefore, DNA vaccines present more promise in communities where large-scale refrigeration is too expensive.
Note: Information sourced from Immunological considerations for COVID-19 vaccine strategies and Recent Advances in Subunit Vaccine Carriers.
How Do Researchers Decide Which Vaccine Type to Use?
The human body has many different ways of fighting illness, and each of these vaccine types are tools that scientists and researchers use to prevent different diseases. Because the immune system and viruses have complex interactions with one another, research and testing are required to identify the technology with the best chance of triggering a lasting immune response to defend against a particular pathogen.
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