Childhood vaccinations: are there too many?

It is frequently heard; we are vaccinating so much. Is it too much? Sometimes accompanied by emotional images of a baby full of needles. What are the current facts and are we vaccinating much more? And if so, is it too much? Every country will have different vaccination schedules, so the numbers of vaccines may differ a bit from country to country and are not absolutes.

(The childhood vitamine K shot is not a vaccine, the importance of providing vitamine K can be found here.)

We, and of course our kids, are constantly exposed to thousands of germs every day. This happens through the food we eat, the air we breathe, and things that our kids especially put in their mouth. This non-pathogenic exposure to germs is healthy and contributes to a well-developed immune system. However, exposure to pathogens is unwanted: there is always a risk, and you really do not need to get ill to become healthier! That would be a very incorrect interpretation of the hygiene hypothesis.

Why vaccination? We are born with an immune system: it is there, it develops, we do not need to interfere. That is all correct in a healthy person. Our immune systems are amazing and protect us every day from attacks. It can fight most pathogens. However, for some of the pathogens we are at elevated risk of encountering, and they are serious. These can cause actual harm, even death. The reason for this can be complex and depend on the attributes of the pathogen. For example, a pathogen can be very quick, outcompeting our slow adaptive immune system that requires 10-14 days to get up to speed. The pathogen can be evasive and trick our immune system by changing its antigens frequently. Just when your immune system is mounting a robust response, the antigens that it recognizes are no longer on the surface of the pathogen, but it has completely changed them! The malaria causing parasite, Plasmodium, is an example of a pathogen that does this. Other pathogens are not dangerous themselves but contain a highly dangerous toxin that in tiny amounts is rapidly detrimental to our health. It short, in all these cases our immune systems can benefit from help!

That is the reason vaccines are strongly recommended; they prepare our immune system to be faster and better when those pathogens are encountered! Vaccines contain tiny amounts of antigens. An antigen being anything that your immune system can recognize. What do those antigens do?

The antigens are presented to your child’s immune cells (B and T cells), the immune cells your child already has made and will be making throughout most part of the adult life as well. The antigens do not "do" anything, do not "make" anything. There are specialized cells, cells that are eating and digesting antigens the entire day and display these at their surface. This is part of your normal "self-checks". The most of these antigens are from you, bits, and pieces that you need to make in the cells of your body. Your immune system is trained not to recognize these. But, pathogens, and thus their bits and pieces in a vaccine, are not you! Your amazing immune system has the capacity to recognize all that is not you; Yes! Really everything, even if it comes from outer space; your immune system will have cells that recognize it. 

But there is the catch! Few cells. You only have a limited amount that can recognize a new antigen. The reason is that you make sufficient B and T cells to be prepared for unknown infections. To catch them all: you make B and T cells, but very few that recognize the same antigen. You will not know if you will ever need that B or T cell if you will ever encounter that antigen. We are prepared for everything, but with lesser amounts. 

So, the antigen in a vaccine, when presented, will select those few cells that recognize this, and only this, antigen: of course, the same antigen that is also part of the pathogen that can cause harm! The selected B and T cells will stimulate you to generate more of them and store them. That is a neat trick! Your immune system has understood that these cells recognize something you have encountered: therefore, you may encounter it again! These cells have proven to be useful for you. Therefore, you will make more, via cell division, and store sufficient in a compartment we call the memory compartment. Having more cells makes you more powerful against an invading pathogen. But that is not all. The immune cells mature; they function better and faster. T cells will develop specialized functions they did not yet have they can now help other cells much better and faster, they can kill infected cells much better and faster. B cells, which make antibodies, will have chosen a better isotype with dedicated functions (IgG, IgA, etc.), they will even have mutated the antibodies to fit the antigen even better. Upon re-encountering the antigen, they make these antibodies super-fast!
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This is how you strengthen the immune system, like encountering the pathogen itself, using the same bodies and cells, but without the danger of not controlling the pathogen!

If we look at children under 2 and take the US CDC numbers. They have nicely compared the current vaccination schedule with that a generation ago, in the 1990s. The previous generation received fewer vaccines, protecting against 8 infectious diseases. These were more complex vaccines, containing over 3000 antigens. These vaccines were certainly good and safe, but there was still room for improvement. Scientific work over the years has made more detailed insights into our immune systems, and our technological progress has allowed new materials to be made and produced at a large scale.
 
The under two years old of today get more advanced vaccines, protecting them from 14 infectious diseases, but they contain only about 300 antigens. So, their exposure to new antigens is much less, their immuun system concentrates more on fewer antigens. This is not necessarily good or bad, it just means a more targeted approach with fewer ingredients.

The ingredients can cause confusion. Vaccines, like any medicine or food, have many ingredients. All are there for a reason!

- Ingredients are added to stabilize (Stabilizers) the antigens, so the vaccine can be stored for a longer time and at higher temperatures. These are commonly found in: food products or naturally in the body and most frequently are: Sugars or gelatin.
- Other ingredients protect against growth of bacteria (Preservatives), again commonly found in food products, and naturally found in fish: frequently used is Thimerosal in flu vaccines.
- Exceptionally low levels of residues from vaccine production can be found in vaccines. There are maximum limits of these set by the national authorities. These include antibiotics from keeping the manufacturing process sterile (antibiotics from the penicillin family are not used due to risk of allergic reactions), cel culture materials such as egg residue (allergy danger), and reagents to kill viruses in inactivated vaccines such as formaldehyde (found naturally in your body, in fruit). 

Deserving special mention are adjuvants. These are compounds especially needed to activate the innate part of your immune system; to mimic there is a pathogen that is dangerous! This important and is a part that determines how well a vaccine works. They can be parts of a pathogen, such as lipids, or even RNA will be a good "danger" signal that alerts your immune system that action is required. Several are found in our surroundings such as drinking water, infant formula, others in health products such as antacids, buffered aspirin, and deodorants. A (in)famous example are aluminum salts. A list of adjuvants in different vaccines can be found here. 

Aluminium salts are added to specific vaccines in small quantities. This is to strengthen the robustness of the immune response due to the ability of aluminium to slowly release antigens. This results in a more prolonged antigen exposure which increases the response. Aluminium for example, a common metal found in air, water, and food, is not readily absorbed by the body, this is exactly the characteristic for which it is used. 

Several of the more recent vaccines do not rely on additionally added adjuvants because these are attenuated virus vaccines or vector/mRNA vaccines; these include: Chickenpox, cholera, COVID-19 (mRNA Pfizer-BioNTech, mRNA Moderna and adenoviral Johnson & Johnson/Janssen and AstraZenica), dengue, Ebola, Hib (ActHIB, HIBERIX), measles, mumps & rubella (MMR), meningococcal (Menactra, Menveo, MenQuadfi), polio (IPOL), rabies, rotavirus, seasonal influenza (except Fluad and Fluad quadrivalent), smallpox and monkeypox (ACAM2000, JYNNEOS), Typhoid, yellow fever, zoster live (Zostavax).

Is there​ such a thing as too many vaccines?
It is clear from the table above; we do vaccinate more. Once there was only smallpox, now other dangerous infectious diseases can be prevented, notably measles, rubella, tuberculosis, hepatitis B, polio, diphtheria, tetanus, pertussis, Hemophilus influenza, Pneumococcus, rotavirus, and human papillomavirus.
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One is excused to think we are at danger to overload our immune system. But there is no truth in this. Once more I need to refer to how amazing the system is. It has billions of B and T cells, and they mostly each have a different antigen they can recognize. It is present from birth, it is active from birth, and it can multitask!

The birth canal gives the first large encounter with bacteria, once delivered into the world, the infant will be immediately targeted by microbes. The outer surfaces such as the skin and the intestine, but also the lungs, will be colonized rapidly. And yes, the little one will manage the onslaught of all these microbes very well: it has an immune system. This highlights that a few vaccines, or 5 at the same time, not an issue is at all.

​One can make calculations how many antigens, and epitopes (the parts of an antigen that ​is actually recognised by a B or T cell) are in a vaccine, how many cells are required to be activated and produce antibodies above the threshold to neutralise a pathogen. Such an approach would indicate that our immune system can deal with 10.000 - 100.000 vaccines at a time. So, 5 or 20 vaccines is a small fraction: it is of no concern.

Of course, we do not base healthcare only on calculations, the simultaneous administration of vaccines has been studied, and shown to be both efficacious and safe (1, 2, 3, 4, 5, 6, 7), and the basis why many are even provided in a single vaccine shot (e.g., DTP and MMR). So, multiple vaccines, as in use, really do not overload your immune system.

Now, you could still claim that it may weaken it. But also, that would be incorrect. Large cohort studies have shown that multiple vaccines have no detrimental effect on for example the frequency or severity of illnesses from non-targeted infections (1, 2): i.e. There is no adverse association between an increasing number of vaccinations and infectious diseases.

To conclude, yes, since the first vaccine against smallpox, the number of vaccines has increased. This has much reduced infectious diseases, childhood mortality, and the resulting health issues in the adult population. The increase in vaccines, which have been improved over the years, has had no negative effect, for healthy individuals, infants, or adults. There is enormous capacity of our immune system to deal with multiple stimuli simultaneously. There is no limit demonstrated for a maximum of vaccinations, with respect to their efficacy and any immune effects against non-targeted disease. It is likely that such a limit does not exist.