Antibodies and immunity: Does vaccine protection last?

In recent times, much of the attention around COVID-19 vaccination has been on waning immunity and the need for boosters. But how does vaccine protection work? And why is it that some vaccines require boosters more often than others?

How is the immune system impacted by vaccines?

The human immune system is a complex and powerful network that actively fights against infection. It consists of many components that work together to defend our body against invaders, such as viruses, bacteria, and other foreign bodies. In general, humans have two types of immunity: innate (general type of protection i.e., the skin barrier) and adaptive (develops throughout our lives from exposure).1

Adaptive immunity, also known as acquired immunity, is the basis for effective immunization and involves immune responses that are specific to an antigen (the part of the pathogen that generates an immune response).1 Vaccines harness the natural immune response and subsequent immune memory to expose the body to an antigen, mimicking a natural infection.2,3 This means that when an individual is exposed to the real life pathogen, the immune response is rapid; thereby, helping to protect the individual from getting infected if the pathogen enters the body.3,4

Vaccines contain antigens that are either derived from the pathogen or are produced synthetically to represent components of that pathogen.5

Why is there variation in immunity?

No matter how a vaccine is developed, every individual’s response to that vaccine is unique.6 As a result, there can be substantial variation in our immune systems in response to vaccination.7 There are several factors that contribute to this, including host factors (e.g., genetics, sex, comorbidities) and vaccine-related factors (e.g., route of administration and vaccine type).7

Why does immunity wane?

The length of protection offered varies between vaccines.3 As a result, the period between booster injections across vaccines also greatly varies. Some vaccines, such as the influenza vaccine, require boosters every year,8 whereas, other vaccines, such as yellow fever, can provide lifelong immunity with a single dose.9 The measles, mumps, and rubella (MMR) vaccine requires two doses, but will protect over 97% of people against measles, and 88% from mumps.10 People who receive MMR vaccination are usually considered protected for life against measles and rubella.10

While scientists do not yet fully understand why some vaccines provide more long-lasting immunity than others, there are several factors that have been found to have an impact11:

  • The rate at which a virus replicates: If a virus replicates quickly, it has a chance to produce more variants. The more variants that emerge, the harder it is to make a vaccine with long-lasting immunity.12,13 Influenza is one example of this. Every year there are multiple new strains of flu, which is why it is recommended for people to get vaccinated annually.12,13
  • The drop in antibody levels: Antibody levels are typically used as an indication of how well a vaccine has worked.14 Antibody levels and short-lived B cells (a type of white blood cell) spike after vaccination, and then drop as cells diminish. Meanwhile, memory B cells and bone-marrow plasma cells (a type of white blood cell developed from B cells that secretes large quantities of antibodies) continue to produce antibodies, but at reduced levels, for decades.14 Identifying the threshold level of antibodies (or other immune-related factors) most closely associated with a vaccine’s effectiveness would allow researchers to determine more precisely when a booster may become necessary, such as in response to waning immunity.14
  • The variation in immune response: The individual’s immune response to initial infection can lead to differing protective levels of vaccination. In other words, the initial response may not develop adequate antibodies, making an additional dose necessary.3

To boost or not to boost?

There are many factors that determine whether to boost or not boost following the original vaccination.15 Some vaccines, such as meningitis16 and diphtheria,17 require booster vaccines as part of vaccination schedules. Whereas others are only necessary for particular groups or when living or traveling in areas where the risk of being infected by a particular disease is high, such as rabies18 and typhoid.19

In some cases, booster vaccines are important to reactivate immune memory and have been shown to result in a rapid rise in antibodies.20 In fact, the quantity and quality of antibodies produced can increase after a booster vaccine.15 More specifically, through a process called antibody affinity maturation, our immune system can learn to better recognize a pathogen and make antibodies that bind more tightly to their target, enhancing the immune response.15 Overall, the aim of a booster shot is to elicit a stronger immune response.14

  1. Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2018 Sep;14(2):1-0.
  2. Sallusto F, Lanzavecchia A, Araki K, Ahmed R. From vaccines to memory and back. Immunity. 2010 Oct 29;33(4):451-63.
  3. Centers for Disease Control and Prevention. Understanding How Vaccines Work. 2022. Available at: [Accessed July 2022]
  4. World Health Organization. How do vaccines work? Available at: [Accessed July 2022]
  5. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021 Feb;21(2):83-100.
  6. Institute of Medicine. Vaccine Safety Forum: Summaries of Two Workshops. Research to identify risks for adverse events following vaccination: biological mechanisms and possible means of prevention. 1997:29-57.
  7. Zimmermann P, Curtis N. Factors that influence the immune response to vaccination. Clin Microbiol Rev. 2019 Mar 13;32(2):e00084-18.
  8. Centers for Disease Control and Prevention. Flu (Influenza). Available at: [Accessed July 2022]
  9. Centers for Disease Control and Prevention. Yellow Fever Vaccine. Available at: [Accessed July 2022]
  10. Centers for Disease Control and Prevention. Measles, Mumps, and Rubella (MMR) Vaccination: What Everyone Should Know. Available at: [Accessed July 2022]
  11. Cohen J. How long do vaccines last? The surprising answers may help protect people longer. Science. 2019 Apr 18;10.
  12. Centers for Disease Control and Prevention. How Flu Viruses Can Change: “Drift” and “Shift”. Available at: [Accessed July 2022]
  13. Wei CJ, Crank MC, Shiver J, Graham BS, Mascola JR, Nabel GJ. Next-generation influenza vaccines: opportunities and challenges. Nat Rev Drug Discov. 2020 Apr;19(4):239-52.
  14. Callaway E. COVID vaccine boosters: the most important questions. Nature. 2021;596(7871):178-80.
  15. Nealon D. The Hazard Gazette. Breaking down boosters. 2021. Available at: [Accessed July 2022]
  16. Centers for Disease Control and Prevention. Meningococcal Vaccine Recommendations. Available at: [Accessed July 2022]
  17. Centers for Disease Control and Prevention. Diphtheria, Tetanus, and Pertussis Vaccine Recommendations. Available at: [Accessed July 2022]
  18. Centers for Disease Control and Prevention. Rabies Vaccination. Available at: [Accessed July 2022]
  19. Centers for Disease Control and Prevention. Typhoid Fever Vaccination. Available at: [Accessed July 2022]
  20. Siegrist CA. Vaccine Immunology. Plotkin’s Vaccines. 2018:16–34.
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