What does “fully vaccinated” against COVID-19 actually mean?
With countries increasingly recommending third or even fourth doses of COVID-19 vaccines, how many vaccine doses will we ultimately need to remain protected against COVID-19?
- 4 April 2022
- 5 min read
- by Linda Geddes
For some pathogens, such as measles or polio, completing the primary vaccination series usually provides lifelong protection against disease. For others, such as tetanus, diphtheria, and pertussis, periodic booster doses of vaccine are required.
When COVID-19 vaccines were first approved for emergency use, the hope was that SARS-CoV-2 would fall into the former category. But as countries that rapidly vaccinated large chunks of their populations soon learned, levels of protective antibodies began to wane over time, resulting in breakthrough infections which, though often not serious, renewed pressure on healthcare systems.
Next-generation COVID-19 vaccines are being developed which could protect against several variants at once, or against multiple coronaviruses. If successful, this could reduce the need for booster doses.
On 30 March, the US Centers for Disease Control and Prevention (CDC) recommended a fourth dose of COVID-19 vaccine for everyone over 50 years of age.
Optimal protection
The CDC still considers people “fully vaccinated” either two weeks after they receive their second dose in a two-dose series (e.g. the Pfizer or Moderna vaccines), or two weeks after their first dose for single-dose vaccines (e.g. the Johnson & Johnson/Janssen vaccine). However, “fully vaccinated” is not the same as “optimally protected”, the CDC said. “To be optimally protected, a person needs to get a booster shot when and if eligible.”
To some degree, this is political: in many countries, whether or not you’re fully vaccinated dictates whether you can enter certain workplaces or travel abroad.
However, even though boosters may currently be needed to ensure high levels of protection against infection, being “fully vaccinated” puts you in a very different category to being unvaccinated, because the full one- or two-dose series remains extremely effective at preventing severe infection and death. Whether people may need boosters further into the future to maintain this level of protection is unclear.
Immune training
COVID-19 vaccines train immune B cells to produce antibodies that attach to different parts of the virus – including neutralising antibodies that attach to the spike protein and stop the virus from infecting cells.
They also stimulate production of T cells – immune cells that identify infected cells and prevent the virus from spreading further.
Waning antibodies
After vaccination, B cells continue to make large amounts of antibodies for a while, but unless they encounter the virus again – either through additional vaccine doses or natural infection – they gradually decrease production, while existing antibodies are naturally broken down and removed from the body. Even so, other, longer-lasting B cells continue to trickle out antibodies, while memory B and T cells patrol the blood for signs of reinfection, ready to rapidly expand if necessary.
In practical terms, this means that if you’re fully vaccinated and encounter the virus, you will rapidly mount an immune response that should keep you protected against severe disease and death, but it may not be enough to prevent a mild to moderate infection, or to stop you transmitting the virus to other people.
Also, because no vaccine is 100% effective, a small minority of fully vaccinated people will still become severely unwell, and a small proportion of them will sadly succumb to the disease.
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Memory boost
This is where booster doses come in. By periodically reminding the immune system what the virus looks like, and teaching it to recognise and remember more parts of the virus, they bolster levels of antibodies and broaden their repertoire, enhancing people’s protection against the original version of SARS-CoV-2 and subsequent variants.
Boosters are particularly helpful in areas with high-infection rates due to low vaccine uptake, and in the context of new and highly transmissible variants. Even if you are fully vaccinated, if you are surrounded by people who are infected with a variant that has learned to overcome vaccine-induced immunity to some degree, there is a greater chance of you also becoming infected.
Also, although the risk of severe illness is small for fully-vaccinated individuals, on a population level, this can still result in significant numbers requiring hospital care, making it harder for health systems to care for people with other diseases and injuries.
Viral differences
Vaccine-induced immunity is complex, and scientists still don’t fully understand why protection against some pathogens lasts longer than others. However, one factor is how quickly the pathogen replicates and acquires new mutations. The more a virus circulates, the quicker it will develop mutations with clinical significance.
Viruses such as SARS-CoV-2 and influenza replicate and mutate quickly, which increases the likelihood of new variants emerging that can overcome vaccine-induced immunity to some extent, meaning boosters are needed – at least for vulnerable populations, such as elderly people. Viruses such as measles and polio are more stable, meaning vaccine-induced immunity lasts a long time.
Another factor is the strength of the immune system response in different parts of the body. Current COVID-19 vaccines are injected into the upper arm, and trigger high levels of antibodies in the blood and other body fluids. However, they are less good at triggering protection in lining of the nasal cavity and respiratory tract – the tissues that SARS-CoV-2 initially infects. Because of this, various researchers are developing nasal COVID-19 vaccines, which could potentially be given as boosters to people who’ve been fully vaccinated.
The numbers game
During vaccine development, scientists do preliminary studies to get an idea of how many doses may be needed, but with the COVID-19 pandemic, time was of the essence. Although it was clear the vaccines were safe and generated high levels of immediate protection, it was impossible to know how long this would last, and whether or how many booster doses would be necessary.
The answer to this is still unclear: it could be one, or many. However, next-generation COVID-19 vaccines are being developed which could protect against several variants at once, or against multiple coronaviruses. If successful, this could reduce the need for booster doses.
Also crucial is how quickly those initial vaccine doses reach people who have not had the opportunity to get fully vaccinated. Until everyone has access to COVID-19 vaccines, the possibility of new variants emerging that could further evade vaccine-induced immunity remains high, spurring demand for booster doses.
