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By: Gurleen Randhawa
Neuroscience Graduate Student
When we think of vaccines, we often picture a quick shot at the doctor’s office, a slight pinch that protects us from harmful pathogens and viruses. But behind every vaccine is a complex and fascinating journey- one that includes innovation, rigorous testing and countless hours of research. Think of your immune system as a marathon runner, always preparing for the next race. In that case, how much does training play a role?
Without a vaccine, when a virus enters your body, it’s a little like running a marathon after being a couch potato all winter- your immune system might catch up eventually, but not without struggle and discomfort. Vaccines are the structured training regimen that trains your body in advance, and prepares your immune system to tackle new and challenging threats with strength and precision.
This analogy of proactive prevention or “training” goes back to the development of the first vaccine in 1796 when a doctor noticed that people who had cowpox were immune to smallpox, which was a widespread and deadly disease at the time. To test this theory, he infected a patient with a small section of a cowpox sore from a milkmaid’s hand, triggering his immune system to respond to the virus. After two months, the individual was re-exposed to smallpox to test his immunity. He remained healthy, becoming the first person to be vaccinated against smallpox. This marked the beginning of modern vaccination and paved the way for the development of future vaccines.
Types of Vaccines- Choosing The Perfect Training Plan
By introducing a small, harmless version of the pathogen, vaccines train the immune system to recognize and respond to future threats.
Live-attenuated vaccines: By using a weakened form of the pathogen, your immune system gets exposure to the full pathogen, allowing you to build endurance. In many cases, these pathogens retain their ability to replicate, triggering a strong immune response. A downside of this, however, is that they may revert back to the pathogenic form, and lead to some severe side effects. This type of vaccine is also challenging to transport, and usually requires a cold chain for stability. On the upside, booster shots are usually not required to maintain protective immunity. The MMR (measles, mumps, rubella) vaccine is an example of a live-attenuated vaccine.
Inactivated vaccines: Kind of like viewing a map of the racetrack before the big day, inactivated vaccines give your immune system a general idea of what to expect. Exposure to a heated or chemically inactivated form of the pathogen elicits a weaker immune response compared to live vaccines and often requires booster shots to achieve protective immunity. However, this does not pose the threat of reverting to the pathogenic form and its much easier to transport! A classic example of this type is the polio vaccine.
Subunit, recombinant and conjugate vaccines: These training plans focus on specific parts of the route. Instead of running the whole course, you train for key challenges, like a steep hill or rough terrain. Subunit vaccines use parts derived from viruses whereas recombinant vaccines mimic natural infections, eliciting a strong immune response. Conjugate vaccines are a subtype of subunit vaccines which are designed against viruses that are not strong enough to trigger an immune response alone. Therefore, they piggyback a section of the virus on a stronger antigen to boost the immune response. For example, the H. influenzae vaccine combines a part of the virus with something stronger, like tetanus toxoid, which leads to a stronger response by the immune system.
mRNA vaccines: This is the cutting-edge training plan, where your immune system gets instructions on how to build its own custom-fit gear to defeat the virus. Most mRNA vaccines don’t introduce a live virus into your body. Instead, they deliver the instructions to make a non-infectious portion of the virus. These mRNA molecules are essentially a recipe, injected into muscle tissue, which is then read by small protein-making factories in our body called ribosomes. Once the protein is made, the mRNA is broken down. The immune system identifies this harmless protein as a warning sign and remembers it in case it ever encounters the actual virus. A well-known example of mRNA vaccines is the COVID-19 vaccine.
Can you design a vaccine for any molecule?
There has been significant research done on developing specialized combinations called hapten-carrier conjugates, which help the immune system recognize and respond to molecules that normally do not trigger an immune reaction. A hapten is like a tag that, on its own, doesn’t do much but when tagged onto a larger carrier molecule, it triggers an immune response.
One of the most interesting examples of this is the development of the cocaine vaccine, an anti-addiction vaccine designed to help individuals struggling with addiction. The idea behind this vaccine is to generate anti-cocaine antibodies to neutralize cocaine in the bloodstream, preventing from crossing the blood brain barrier and reaching the central nervous system. Without access to the brain, the drug’s pleasureable effects are blocked. Because of cocaine’s small size, it can easily pass through to the brain, but when combined to a large bacterial protein and injected into the blood, the immune system is triggered and generates antibodies against cocaine. In subsequent uses, these antibodies neutralize the drug before reaching the brain. The vaccine has not been successful as a stand-along strategy, but in combination with other treatments, it may help cocaine-dependent individuals quit. Similar vaccines are being developed against nicotine.
Building the Training Plan- Steps in Developing a Vaccine
Efficacy and Side Effects of Vaccines
How is vaccine efficacy measured? In the past, efficacy has been measured by a vaccine’s ability to prevent disease. However, the way we measure efficacy has changed over time. This explanation is still relevant for some diseases. But for others, such as COVID-19, the efficacy of a vaccine is measured as its ability to reduce disease severity.
Side effects can occur with any vaccine because you are trying to induce an immune response in your body. Just like running a marathon, you are likely to feel tired, achy and maybe a little nauseated. More severe side effects, such as inflammation and allergic reactions, happen rarely but are treatable conditions. All vaccines pose a risk of potential side effects. However, so does contracting an infection.
Overall, vaccines are one of the greatest achievements in medicine, having eradicated several deadly diseases like smallpox and polio, saving millions of lives. Ongoing research into vaccines for diseases such as Japanese encephalitis, an illness prevalent in Asia, gives us optimism for future advancements and treatments. In today’s complex global health landscape, understanding how vaccines are developed is essential for making informed decisions. If you have any questions or concerns about the safety of certain vaccines, it’s a good idea to consult with a healthcare professional to get more information.
References
Abo, Y.-N., Jamrozik, E., McCarthy, J. S., Roestenberg, M., Steer, A. C., & Osowicki, J. (2023). Strategic and scientific contributions of human challenge trials for vaccine development: facts versus fantasy. Lancet. Infectious Diseases/˜The œLancet. Infectious Diseases, 23(12), e533–e546. https://doi.org/10.1016/S1473-3099(23)00294-3
Graham, B. S., Mascola, J. R., & Fauci, A. S. (2018). Novel vaccine technologies: essential components of an adequate response to emerging viral diseases. JAMA, 319(14), 1431-1432.
Havlicek, D. F., Rosenberg, J. B., De, B. P., Hicks, M. J., Sondhi, D., Kaminsky, S. M., & Crystal, R. G. (2020). Cocaine vaccine dAd5GNE protects against moderate daily and high-dose "binge" cocaine use. PloS one, 15(11), e0239780. https://doi.org/10.1371/journal.pone.0239780
Pollard, A. J., & Bijker, E. M. (2021). A guide to vaccinology: from basic principles to new developments. Nature Reviews. Immunology, 21(2), 83–100. https://doi.org/10.1038/s41577-020-00479-7
Other References:
https://www.cdc.gov/vaccines/basics/how-developed-approved.html
https://coronavirus.jhu.edu/vaccines/timeline
https://www.who.int/news-room/feature-stories/detail/how-are-vaccines-developed
https://www.who.int/news-room/spotlight/history-of-vaccination/a-brief-history-of-vaccination