Vaccines, the immune memory trick

“With the exception of safe water, no other modality… has had such a major effect on mortality reduction and population growth.” – Susan and Stanley Plotkin, Vaccine 5^th ed (2008).¹

In 1979, the World Health Organization (WHO) declared the deadly disease smallpox, which had killed an estimated 300 million people worldwide in the 20^th century alone, to be eradicated². Presently, other lethal diseases, such as measles and polio, that were historically responsible for millions of deaths^3,4 are also on the path to eradication – in Canada, the number of cases has fallen by 99% since the 1920s⁵. These successes are key examples of how modern vaccination has contributed to the improvement of human health.

Vaccines take advantage of a feature of our adaptive immune system called immunological memory. This refers to the ability of B and T cells of the immune system to “remember” foreign agents that they have previously encountered. During the normal course of an infection, immunological memory is acquired by our B and T cells against the invading microbe, also known as a pathogen. This memory ensures that B and T cells can recognize and fight off the same agent in the future. However, some pathogens can cause serious disease, and infected individuals may suffer severe symptoms before memory is established. Vaccination artificially induces immunological memory against a disease-causing pathogen by using an innocuous variant or component to simulate a real infection. By educating our immune systems with a harmless pathogen substitute in the form of a vaccine, our bodies can gain immunity without ever being exposed to the real deal.

Vaccines come in different forms developed for different kinds of pathogens and have shown great efficacy in reducing cases and mortalities when implemented consistently. According to the WHO, vaccination has prevented at least 10 million deaths globally from 2010 to 2015⁶.

The effectiveness of vaccines is experienced not only by immunized individuals, but also at the population level. A transmittable pathogen is less likely to spread between people when most of the population is immune, thereby extending protection to vulnerable members of the community⁷. This effect is called herd immunity, and its importance has become increasingly relevant in recent years due to an increasing trend in parents choosing not to vaccinate their children. This has resulted in several local outbreaks of measles in the United States despite the disease having been declared eliminated in the country in 2000⁸. There are also concerns that the incidence of other vaccine-preventable diseases will rise in the near feature, as many parents are choosing not to complete routine vaccinations for their children amidst the COVID-19 pandemic caused by the SARS-CoV2 pathogen⁹.

Current challenges and the future of vaccine development

Despite their undeniable success in controlling the spread of infectious disease, there is still an unmet need for vaccines with regards to diversity and accessibility. In addition to the difficulty of developing effective vaccines for diseases such as HIV and influenza^10-13, current vaccine developmental pipelines also hinder efficient production and delivery of vaccines to areas of need^12,13. For example, Southeast Asia, Eastern Mediterranean, and Africa combined received only 5% of global influenza vaccine doses in 2015¹². Rapid mutation rates of some viruses can also quickly render vaccines obsolete, requiring routine re-vaccination for protection such as in the case of the seasonal flu^10,12.

Another major technical challenge is the length of time it takes to produce a new vaccine. With the current technology, a successful vaccine takes an average of over 10 years to go from development to the market¹² – too slow to combat emerging novel pathogens like SARS-CoV2. Nucleic acid vaccines are a relatively new area of vaccine technology that may address this shortcoming. Nucleic acid sequences like DNA or RNA are used as the vaccine, which act as a blueprint for our cells to create the protein component that elicits immune memory¹². Compared to traditional vaccines, the same production platform can be used to generate new vaccines by simply customizing the nucleic acid sequence¹². This drastically shortens the production length by bypassing the need for individualized production and quality control steps that must be specifically designed for each unique pathogen- or protein-based vaccine¹². This new technology is being put to the test in the COVID-19 pandemic, with 2 nucleic acid vaccine candidates currently in clinical trials. These challenges and new advances highlight the room for growth in vaccine development, which will be key in fighting future threats against human health.

Works cited

1. Plotkin SL, & Plotkin SA. (2008). A short history of vaccination. In SA Plotkin, WA Orenstein, & PA Offit (5th ed.), Vaccine. Elsevier Inc.
2. World Heath Organization. (2011). Bugs, drugs and smoke: stories from public health.  https://www.who.int/about/history/publications/public_health_stories/en/
3. World Health Organization. (2019). Measles. https://www.who.int/news-room/fact-sheets/detail/measles
4. World Health Organization. (2019). Poliomyelitis. https://www.who.int/news-room/fact-sheets/detail/poliomyelitis
5. Public Health Agency of Canada. (2018). Vaccines work [Infographic]. Effectiveness of vaccination for 6 diseases in Canada https://www.canada.ca/en/public-health/services/publications/healthy-living/vaccines-work-infographic.html
6. Chan M. (2017). Ten years in public health 2007-2017. World Health Organization. https://www.who.int/publications/10-year-review/vaccines/en/
7. Meissner HC. (2015). Why is herd immunity so important? AAP News, 36(5): 14.
8. Peeples L. (2019). Rethinking herd immunity. Nat Med, 25: 1178-80.
9. Weeks C. (2020). Doctors across Canada seeing a drop in number of routine vaccinations. The Globe and Mail. https://www.theglobeandmail.com/canada/article-doctors-across-canada-seeing-a-drop-in-number-of-routine-child/
10. Houser K, & Subbarao K. (2015). Influenza vaccines: challenges and solutions. Cell Host Microbe, 17(3): 295-300.
11. Barouch DH. (2008). Challenges in the development of an HIV-1 vaccine. Nature, 455(7213): 613-9.
12. Rauch S, Jasny E, Schmidt KE, & Petsch B. (2018). New vaccine technologies to combat outbreak situations. Front Immunol, 9: 1963.
13. Bakker LG, et al. (2020). The complex challenges of HIV vaccine development require renewed and expanded global commitment. Lancet, 395(10221): 384-8.

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Karen Yeung

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