Why do we develop lifelong immunity to some diseases but not others?

Because of vaccines, once-prevalent, deadly diseases like measles, smallpox, and polio are now hardly ever seen in the developed world.

The World Health Organization estimates that 2-3 million lives are saved each year from vaccination programs.¹ ² For most, these vaccines were administered to us in childhood and give us immunity for life without the need for follow-up booster shots.

For other diseases, like the flu (and most recently COVID-19), it's a totally different story. Annual booster vaccinations are the norm for staying protected against these quickly-evolving strains. And new research is suggesting that its level of effectiveness may even start waning within a season (about 90 days).³

So why is it that some vaccines are able to provide us with lifelong immunity to some diseases, but not others? It turns out that the answer is more complicated than we thought. And it's something that researchers are still in the process of figuring out to make all vaccines better.

To understand what we know so far about vaccine durability, we first need to understand how our body's immune system works.

Different types of immunity

Our immune system is made up of different types of protective systems that work together to keep our bodies safe from external pathogens (organisms that can cause diseases) like bacteria and viruses.

At the broadest level, our immune system can be classified in terms of innate and adaptive immunity.⁴ ⁵ ⁶

• Innate immunity is the immunity that we're born with and consists of various external (e.g. skin) and internal (e.g. cellular) defences. The cellular defences at this level are often non-specific — it responds the same way to all potential threats. Think of them as the first-responders in an emergency.

• Adaptive immunity is the immunity that we are not born with and must be developed over our lifetime. Under this category, we can further split it into active and passive immunity.

  • Active immunity refers to our body's immune reaction after exposure to a disease. This can occur naturally as our body develops specific antibodies to combat the individual pathogen. These antibodies can also be artificially built up through vaccines.

  • Passive immunity is the immunity that we get from something external to us. This can be the antibodies that we receive from our mothers at birth. Or it can be acquired through artificial means like immune-boosting blood treatments.

How our natural active immunity protects us

In this article, we're most interested in natural and vaccine-triggered active immunity. And the process starts with each pathogen having a unique "thumbprint" called an antigen. The antigen is what signals our body to produce an immunologic response to fight it off — involving the B and T cell lymphocytes (white blood cells). B and T cells have a wide variety of functions. But to put it simply, B cells are generally involved with the production of antibodies to destroy or block pathogens. The type of B cells that produce antibodies are called plasma B cells.

On the other hand, T cells help to support the B cells in their antibody production processes and kill off other cells that have already been infected by the pathogen.⁷ ⁸ ⁹

Unlike innate immunity which simply attacks all foreign objects in the same way, the antibodies produced by our active immunity are specific to different pathogens' antigens. This means that the antibody for "pathogen A" will be ineffective for "pathogen B". But in some cases, our immune system can produce a similar response if the pathogens have closely-related structures.

The interesting thing about our immunity is that it also never really forgets after the first time it's been attacked. When first introduced to a new pathogen, the body takes time to recognize the intruder and produce antigen-specific antibodies. Through that process, it can result in serious illness.

But once the immune system has had experience with a certain pathogen, it can create memory B and T cells that keep the body prepared for the next invasion. In the event where it encounters the same pathogen again, these memory cells initiate an immune response in a much faster and stronger way. Thus, increasing the chances of long-term protection from the disease.⁷ ¹⁰

How do vaccines keep us immune to diseases?

Vaccines work by re-creating this immunological memory but without the threat of serious illness or death.¹¹ Different vaccines do this in various ways. But the most basic type is created by inactivating or weakening the pathogen and introducing it to the person. The key part to this is making it inactive so that it will not cause illness.

But it must still contain the antigen that will elicit antibody production so that it can be used when the real pathogen is encountered —  kind of like getting the weapons ready before the invaders attack.⁷

More recently, mRNA vaccines used for COVID-19 don't contain any virus at all. But the same underlying goal is still achieved of creating an antibody response in the body in preparation for a real infection. 

Why do I need boosters for some vaccines but not others?

Similar to our natural active immunity, vaccine-induced immunity also undergoes the learning process of developing memory cells. So why is it that some vaccines seem to elicit a better learning response and grant us life-long immunity? While others sometimes require yearly boosters — like the flu jab?

How long a vaccine lasts comes down to various factors. And unfortunately, there are still many gaps in our knowledge about how to create the ideal conditions for long-term vaccine-induced immunity across different diseases. However, here's what we know so far:  

Antibodies have different decay rates, and memory cells take time to develop

Firstly, antibodies don't last forever and their rate of decay matters. For diseases like measles, this rate is relatively slow. The antibodies seem to stick around for longer and vaccine-induced immunity remains quite durable over time.

For some other vaccines (like the one for tetanus), the antibodies get broken down faster. Scientists combat this with booster shots to cause a larger immune response to make up for its faster decay so that the overall threshold for protection is still met over time.¹² ⁷

Sometimes, memory cells also take time to develop and they only work in the presence of an infection or vaccine. If the vaccine from the first dose has waned, memory cells stop working. So boosters are there to also make sure that the memory cells stay active.¹³

Type of vaccine technology matters

Different types of vaccine technology also affect how well our body is able to create long-term immunity.

In general, live (but weakened) replicating viral vector vaccines tend to elicit a more durable immune response compared to vaccines that use non-replicating, dead pathogens. Because they’re "alive" this makes them very similar to natural infection and creates a more robust immune response. This is the technology used to protect against measles and grants life-long immunity. The issue with this type of vaccine is that because it so closely resembles the real pathogen, it can cause illness — especially in immunocompromised people.¹⁴ ¹⁵

To overcome this risk, scientists have developed a newer type of non-replicating vaccine that is a mid-way between the live-weakened and inactivated types. They're called virus-like particles (VLPs). They're artificially formulated to have the outer protein structure of a virus. But they don't contain any genetic material.

The lack of any genomic information means that there is no risk of unintended infection or mutation.¹⁶ ¹⁷

The amazing thing about VLPs is also how effective it is. It was first created to combat human papillomavirus (HPV) — a sexually transmitted disease that's linked to various cancers. Ever since it's been administered in the early 2000s, there have been no signs of waning immunity so far.¹³ ¹⁸

Experts attribute the effectiveness of the VLPs to their close external resemblance to real pathogens. This allows the immune cells to efficiently recognize it and produce a corresponding reaction efficiently.

Why the immune response lasts longer is a trickier question to answer. But what researchers have noticed is that VLP vaccines tend to make B memory cells produce a special type of antibody-producing cell called long-lasting plasma cells (LLPCs). LLPCs are able to stay in the bone marrow for years and continue producing antibodies long after the vaccine or infection is gone.¹⁹ ²⁰

Because of this, there has been a lot of interest in using VLPs to protect against other diseases. But many questions still remain about how exactly they manage to ramp up the body's production of LLPCs. Answering this will likely be the key to making other vaccines more durable as well.

Viruses mutate at different rates

Another issue confounding a vaccine's long-term effectiveness relates to how quickly pathogens are able to mutate. The flu virus is a common case of a quickly evolving pathogen, and these mutations happen as a result of 2 main processes — antigenic drift and antigenic shift.

In the case of antigenic drifts, small errors are made in the copying of genetic code when the virus replicates itself.

And this results in changes to how the antigen structure is expressed. Antigens play a key role in helping our immune system to recognize pathogens — kind of like a thumbprint. So if the antigen structure has changed, the pathogen is able to go undetected by our immune system.

For antigenic shifts, two related viruses meet and share genetic material to produce a whole new subtype of virus.

This causes the same effect of allowing the pathogen to be unrecognizable. But it happens less frequently and the changes that occur are more significant. These shifts are also more likely to result in pandemics.²¹

So if a virus tends to mutate frequently, our vaccines will need to be updated more often through boosters to maintain protection. 

What this means for people who want to stay protected from diseases

Should you take booster shots?

If public health bodies recommend booster shots for a specific disease, it means that the unique qualities of the vaccine and pathogen require it.

We shouldn't assume just because one vaccine doesn’t need booster shots, that others will be the same.

It’s also important to keep in mind that vaccine recommendations can change over time. For example, the US has seen outbreaks of mumps over the past decade even though it was almost eradicated. As a result, the Centers for Disease Control and Prevention (CDC) now recommends that at-risk adult groups may need to take extra shots.²² ²³

So it's critical to listen out for the latest public health announcements to ensure that you stay protected from preventable diseases. 

Does boosting your natural immunity give you further protection?

Staying up to date with the recommended vaccination schedules of local health authorities is the best way to "boost" your immune system. But how about natural methods — like taking herbs or eating certain foods?

Based on current scientific research, there is not enough evidence to suggest a direct link between specific lifestyle choices and immunity enhancement. Even the widely held belief that Vitamin C supplements help to combat the common cold is not strongly substantiated by research. At most, it only reduces the length of a cold by a day.²⁴ ²⁵

However, experts still suggest that having a generally healthy and balanced lifestyle plays an important role in the functioning of the immune system. This includes:

• Eating lots of vegetables and fruits.

• Not smoking.

• Getting regular exercise.

• Getting sufficient sleep. 

• Drinking alcohol in moderation.

• Minimizing stress.

• Practising good hygiene — frequent hand washing.

We still have a long way to go in understanding how to make all vaccines last longer. But until then, booster shots for certain vaccines will be the best way to ensure that we stay protected from diseases.

Sources:

1. Diseases you almost forgot about (thanks to vaccines) | Centers for Disease Control and Prevention

2. Vaccines and immunization | World Health Organization

3. Early bird gets the flu: What should be done about waning intraseasonal immunity against seasonal influenza? (2019)

4. What you need to know about acquired immunity | Healthline

5. Innate vs adaptive immunity | Technology Networks

6. Immunity types | Centers for Disease Control and Prevention

7. How do vaccines work? | World Health Organization

8. Immuno-inspired robotic applications - a review | Research Gate

9. Overview of b- and t-cell function | MSD Manual Professional Version

10. Coronavirus: b cells and t cells explained | The Conversation

11. From vaccines to memory and back (2010)

12. Some vaccines last a lifetime. Here’s why covid-19 shots don’t. | The Wall Street Journal

13. B cell memory: understanding COVID-19 (2021)

14. Replicating and non-replicating viral vectors for vaccine development (2007)

15. Vaccine types | HHS.gov

16. Production of virus-like particles for vaccines (2017)

17. How long do vaccines last? The surprising answers may help protect people longer | Science

18. HPV vaccine information for young women | Centers for Disease Control and Prevention

19. Why do antibodies fade after a COVID-19 infection, and will the same thing happen with vaccines? | The Conversation

20. How long do vaccines last? The surprising answers may help protect people longer | Science

21. How do viruses mutate and what it means for a vaccine? | Pfizer

22. Mumps cases and outbreaks | Centers for Disease Control and Prevention

23. Measles, mumps, and rubella (MMR) vaccination: What everyone should know | Centers for Disease Control and Prevention

24. How to boost your immune system | Harvard Health Publishing

25. By the way, doctor: What's the right amount of vitamin C for me? | Harvard Health Publishing

The author, Dawn Teh, is a health writer and former psychologist who enjoys exploring topics about the mind, body, and what helps humans thrive.