What is waning immunity after vaccination?

How do vaccines produce immunity?

Vaccines offer both short and long-term protection or ‘immunity’ against infectious diseases.

In the days and weeks following vaccination, there is an initial surge in immune cells and antibodies that act as the ‘frontline fighters’ against a foreign invader in the body, such as a virus.1 Over time, these ‘frontline fighters’ naturally fade or wane, but they don’t reduce to zero.1 This is normal, expected and happens with all vaccines.1

Following this initial response, the immune system is still primed to ‘protect’, with longer-lasting ‘memory’ B and T-cells remaining in the body – ready to produce antibodies and defend against the disease if it’s later encountered.1,2
 

How is ‘lasting immunity’ measured?

Different studies are used to measure how well a vaccine works, and the duration of protection they provide.3 For example:  

  • Efficacy studies look at a vaccine’s ability to prevent disease (e.g. infections, hospitalisations or deaths) in a controlled research setting.
  • Effectiveness studies look at how well a vaccine performs in the ‘real-world’, often in much larger, more diverse populations and geographies.
  • Immunogenicity studies are a more complex measure, looking at the specific immune response a vaccine triggers and how long it lasts.4 Scientists study antibodies and T-cells for example, looking at how they interact in the body and the levels that might protect from illness.5,6,7

Immunogenicity studies can also measure whether there’s a decline in antibodies over time, or ‘waning immunity’. The exact duration of immunity varies with different diseases and different vaccines.8 Importantly, a drop in antibodies following vaccination doesn’t necessarily mean a greater risk of serious illness, thanks to the body’s ‘memory’ B and T-cells.
 

Why do some vaccinated people still get infected?

Following vaccination, some people may experience ‘breakthrough infection’ – where they still get the virus or illness despite being fully vaccinated. This is more likely if high levels of viruses are circulating in a population, or if certain viral variants are particularly contagious.9,10 No vaccine is 100% effective so some breakthrough infections are expected. Importantly, they don’t mean the vaccine isn’t working. The role of many vaccines is to prevent serious illness and death, not infection altogether.11 If breakthrough infections do occur in vaccinated people, the symptoms are usually less severe and may result in fewer hospitalisations and deaths than infections in those who are unvaccinated.10,12

What ‘level’ of immune response is needed to fight future infection?

Using knowledge and evidence gained from immunogenicity studies, scientists can establish the levels and mix of antibodies and T-cells a vaccine needs to trigger to prevent serious illness. These are called the ‘correlates of protection’.

In addition to what is already known from efficacy trials and real-world evidence, defining the ‘correlates of protection’ can help to determine:13

  • how well a vaccine is working (at a biological level)
  • if there are certain individuals who are more susceptible to an illness or virus and whether additional protective measures are needed
  • if there’s a need for additional vaccine doses or ‘boosters’
  • the overall immunity of a population, which can help guide public health decisions.
     

Are booster vaccines necessary?

For many infectious diseases, additional doses or ‘boosters’ are a standard part of the vaccination schedule. For example, booster vaccines are given for tetanus, diphtheria and polio.14 Boosters can help to elevate the level of antibodies and memory immune cells, and in some instances, strengthen their potency.1

There are several considerations when assessing whether ‘mass’ booster vaccination programmes are required. Firstly clinical need – looking at the level of immunity achieved following vaccination, and whether it still gives adequate protection against serious illness.1,15 Other considerations include how well a booster dose might work, optimal timing, use in different populations and geographies, feasibility and equitable distribution of vaccine supply.15

Decisions on whether or not a booster is required should be led by examining all the scientific evidence available. Until a defined protective threshold or ‘correlate of protection’ is known, and sufficient evidence exists for ‘real world’ vaccination effectiveness over time, it’s difficult to determine whether a booster vaccine is needed to provide continued, protective immunity.1,15


References

1. Callaway E. COVID vaccine boosters: the most important questions. Nature. 2021. Available at: https://www.nature.com/articles/d41586-021-02158-6. Last accessed September 2021.

2. World Health Organization. How do vaccines work? Available at https://www.who.int/news-room/feature-stories/detail/how-do-vaccines-work. Last accessed September 2021.

3. World Health Organization. Guidelines on clinical evaluation of vaccines: regulatory expectations. 2016. Available at https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf. Last accessed September 2021.

4. Mahanty S, Prigent A, Garraud O. Immunogenicity of infectious pathogens and vaccine antigens. BMC Immunology. 2015; 16 (31).

5. British Society for Immunology. Immune responses to viruses. Available at https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses. Last accessed September 2021.

6. Wajnberg A, Amanat F, Firpo A, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020; 370, 1227–1230.

7. Slota M, Lim JB, Dang Y, et al. ELISpot for measuring human immune responses to vaccines. Expert Rev Vaccines. 2011;10(3):299-306.

8. The Immunisation Advisory Centre. Efficacy and effectiveness. Available at https://www.immune.org.nz/vaccines/efficiency-effectiveness. Last accessed September 2021.

9. Centres for Disease Control and Prevention. COVID-19 Vaccines Work. Available at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/work.html. Last accessed September 2021.

10. Centres for Disease Control and Prevention. The Possibility of COVID-19 after Vaccination: Breakthrough Infections. Available at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/why-measure-effectiveness/breakthrough-cases.html.
Last accessed September 2021.

11. Pollard A, Bijker E. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021; 21: 83–100.

12. MIT Medical. Breakthrough infections: What you need to know. Available at: https://medical.mit.edu/covid-19-updates/2021/08/breakthrough-infections. Last accessed September 2021.

13. Krammer F. A correlate of protection for SARS-CoV-2 vaccines is urgently needed. Nature Medicine. 2021; 27: 1147-1148.

14. NHS. 3-in-1 teenage booster overview. Available at https://www.nhs.uk/conditions/vaccinations/3-in-1-teenage-booster/. Last accessed September 2021.

15. World Health Organization. Interim statement on COVID-19 vaccine booster doses. Available at https://www.who.int/news/item/10-08-2021-interim-statement-on-covid-19-vaccine-booster-doses. Last accessed September 2021.


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Veeva ID: Z4-37582
Date of Preparation: October 2021