The Science Behind the Annual Flu Vaccine – Could COVID-19 Be Next?

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Written by Amelia Allen '27

Edited by Andrew Ni ‘26

As you plan your autumn activities, remember to book your annual flu shot, and get used to booking a Covid-19 shot too. You may be questioning why you need a flu shot annually when some vaccines for diseases like Varicella, commonly known as Chickenpox, only need to be administered twice to protect you for life [1]. Why doesn’t your flu shot from three years ago protect you this flu season? The reason is that unlike more stable viruses, the flu continuously evolves every year into new strains.

The flu, more formally known as influenza, mutates in two ways: “antigenic drift,” which is gradual changes to the virus, and “antigenic shift,” which is a larger, more rapid change. In the rare case of antigenic shift, pandemics ensue. However, vaccine developers normally anticipate and create yearly vaccines based on antigenic drift as it can be presumed that the flu virus will mutate every year [2]. In terms of frequency, the influenza virus continually mutates as it infects people’s cells, to the point where small mutations occur in every person who becomes infected [3].

To explore more in depth how influenza evolves, we must explore the structure of the influenza virus. The surface of the influenza virus has two prominent proteins, Hemagglutinin (HA) and neuraminidase (NA); these are “attachment proteins,” meaning they are the virus’s tool to attach onto your body’s cells with the purpose of taking over your cells to replicate more of the virus [4,5]. HA and NA can also be classified as antigens, which are proteins that the body identifies as unfamiliar, prompting an immune response [6].

The immune system response can be broken into two categories, innate and adaptive [7]. The innate immune system is triggered first and begins with a type of white blood cell, known as a macrophages, consuming the antigens and breaking them into fragments. Next, the adaptive immune response begins and primarily relies on two other types of white blood cells, T cells and B cells. The T cells identify the antigens and prompt the B cells to release antibodies [6]. Antibodies are proteins that bind to antigens. Once bound, antibodies have the dual effect of disabling the virus from entering the body’s cells and signaling other cells to break down antigens [7]. Once the immune response succeeds in getting rid of the virus, most of the T cells and B cells die off; however, a portion of each remain and become memory T cells and memory B cells, which remember how to deal with the virus and can trigger an immune response in a much shorter period of time if the virus enters the body again [8].

Similarly, vaccines are designed to contain antigens that mirror those of a virus. T cells do not know the difference between an antigen fragment from a virus and an fragment antigen from a vaccine, so the process of signaling B cells, creating antibodies, and gaining memory T cells and B cells remains the same [6].

Despite the body developing memory T and B cells to combat HA and NA, the influenza virus mutates to become resistant to vaccines by changing the structure of these HA and NA proteins so the antibodies made by the memory B cells can no longer bind. These random mutations selected for by evolutionary pressure circumvent the body’s ability to fight against the virus [4]. In response to influenza mutations, virologists collect samples to identify the new and widespread strains of influenza, determine what strains to target, and grow the virus in a controlled environment. The vaccine is produced through killing the lab-grown virus in a way that maintains the HA and NA antigens for the immune system to respond to [9]. Ultimately, if a person becomes infected with the real, live virus, the memory T and B cells produced due to the vaccine will be able to respond quickly and make antibodies to kill the virus.

Understanding the need for an updated vaccine to combat evolved strains of influenza can help us prepare for COVID-19. There have been several booster shots available the past few years following the original vaccine in 2020. This year, the COVID-19 vaccine being offered is not a booster shot but rather an updated vaccine [10]. The purpose of booster shots are to increase antibodies after the ones produced due to diminishing effects of the vaccine. For example, the 2022 booster shots were updated to be “bivalent”, meaning they target both the original strain of the virus that the original vaccines were designed for plus the Omicron strain, which was new at the time [11]. Conversely, this year's vaccine is an updated vaccine, so instead of boosting to protect against old strains, it is a new formula that targets strains that descend from the JN.1 variant, specifically KP.2 [10]. This is similar to how flu vaccines are updated each year to match the new strains. Getting vaccinated for COVID-19 and its subsequent strains is preferable to waiting to contract COVID-19 for a boost in natural immunity because vaccination increases the likelihood of an asymptomatic case and decreases the chance of getting long COVID [12].

In summary, flu shots are needed every year to account for the influenza virus’ continual mutations. Flu vaccines expose our bodies to a dead version of the virus to equip cells to remember how to respond to the actual virus and prevent fatal effects. As we recognize that COVID-19 is here to stay and we will likely keep having new strains, knowing why some vaccines are annual will emphasize the importance of staying up to date on COVID shots. So don’t forget to schedule both your shots to have a fun and healthy fall!

References

1. CDC. “Chickenpox Vaccination,” August 21, 2024. https://www.cdc.gov/chickenpox/vaccines/index.html#:~:text=Most%20people%20who%20are%20vaccinated,children%2C%20but%20not%20for%20all.

2. CDC. “How Flu Viruses Can Change: ‘Drift’ and ‘Shift,’” September 17, 2024. https://www.cdc.gov/flu/php/viruses/change.html?CDC_AAref_Val=https://www.cdc.gov/flu/about/viruses/change.htm.

3. Brody Marcus, Mary. “Why Seasonal Flu Evolves Faster Than We Can Fight It.” Duke University, March 29, 2020. https://globalhealth.duke.edu/news/why-seasonal-flu-evolves-faster-we-can-fight-it.

4. Shao, Wenhan, Xinxin Li, Mohsan Goraya, Song Wang, and Ji-Long Chen. “Evolution of Influenza A Virus by Mutation and Re-Assortment.” International Journal of Molecular Sciences 18, no. 8 (August 7, 2017): 1650. https://doi.org/10.3390/ijms18081650.

5. Maginnis, Melissa S. “Virus–Receptor Interactions: The Key to Cellular Invasion.” Journal of Molecular Biology 430, no. 17 (August 2018): 2590–2611. https://doi.org/10.1016/j.jmb.2018.06.024.

6. Institute of Medicine (US) Board on Health Promotion and Disease Prevention. Vaccine Safety Forum: Summaries of Two Workshops. Washington (DC): National Academies Press (US); 1997. Immune Response to Vaccine Antigens. Available from: https://www.ncbi.nlm.nih.gov/books/NBK233000/

7. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Chapter 24, The Adaptive Immune System. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21070/

8. Adenike Shittu. “Understanding Immunological Memory.” American Society For Microbiology, March 11, 2023. https://asm.org/articles/2023/may/understanding-immunological-memory.

9. Gerdil, Catherine. “The Annual Production Cycle for Influenza Vaccine.” Vaccine 21, no. 16 (May 1, 2003): 1776–79. https://doi.org/10.1016/S0264-410X(03)00071-9.

10. FDA. “FDA Approves and Authorizes Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants,” August 22, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-and-authorizes-updated-mrna-covid-19-vaccines-better-protect-against-currently.

11. Lin, Dan-Yu, Yangjianchen Xu, Yu Gu, Donglin Zeng, Bradford Wheeler, Hayley Young, Shadia K. Sunny, and Zack Moore. “Effectiveness of Bivalent Boosters against Severe Omicron Infection.” New England Journal of Medicine 388, no. 8 (February 23, 2023): 764–66. https://doi.org/10.1056/NEJMc2215471.

12. Francis Collins. “Breakthrough Infections in Vaccinated People Less Likely to Cause ‘Long COVID.’” NIH Director’s Blog (blog), September 14, 2021. https://directorsblog.nih.gov/2021/09/14/breakthrough-infections-in-vaccinated-are-less-likely-to-cause-long-covid/.