“What’s In A Vaccine?”

Nov 1

I appeared on a podcast where I explained a lot of things about how vaccines work, mostly considering what was in them and why it was there. These are the show notes I wrote up discussing the topic.

How do vaccines work?

In the broadest possible terms, vaccines work by simulating an infection. They supply antigens (the thing we want the immune system to respond to- for instance a protein on the surface of a virus, or a sugar from a bacterial capsule) to induce correlates of protection. Correlates of protection refer to things we can measure which are statistically associated with being protected, for instance antibodies or T cells. We can measure the level of antibodies in an individual against a particular antigen to see whether or not they are protected against that antigen. This is how most vaccines work- they induce high titers of antibodies that go on to prevent infection. In some cases, the correlate we are measuring is the thing that is itself doing the protecting (don’t worry though- the process of measuring cannot meaningfully affect the quantity of that correlate to an extent that it could render you unprotected).

The immune system constantly faces a number of challenges from the environment in ensuring that the host is protected, constantly having to fend off assault from various microbes but also maintain equilibrium with the community of microbes that are beneficial to our health (the microbiota). How is this accomplished? The earliest framework to explain this was the self vs. non-self model which held that the immune system had the ability to rapidly identify self and non-self species and would react in a defensive fashion against non-self and eliminate them. In more formal terms, the immune system recognizes pathogen-associated molecular patterns (PAMPs) which would then go on to induce immune responses, and does not respond to self. This framework does explain quite a bit, like for example why we may reject transplanted organs from someone genetically different from us. There’s a problem here though: the microbes colonizing us also have these same pathogen-associated molecular patterns. Plus, a healthy immune system has to be able to respond to self too, as it does in viral infection, for example. Janeway and Matzinger advanced a more elegant theory which held that there had to be additional context- danger. When damage to the tissues occur, as happens with infection, alarmins (sometimes also called damage-associated molecular patterns, or DAMPs) are released, triggering inflammation. PAMPs refer to foreign molecules which can go on to activate the immune system, essentially regardless of context (danger or not). For example, some bacteria have a substance called lipopolysaccharide (LPS) and even a very small amount of it is capable of inducing inflammation so potent that it causes systemic inflammatory response syndrome (SIRS), a condition in which widespread inflammation results in damage to the body’s tissues that even leads to organ dysfunction or organ failure. DAMPs on the other hand are our own molecules, which have been misplaced to compartments they should not be found in. For example, RNA is normally not supposed to be present outside the nuclei of our cells, but if a cell dies, it can be released, indicating damage. Pattern recognition receptors (PRRs) recognize PAMPs and DAMPs and induce inflammation that will result in immune responses.

What are antibodies?

Most vaccines are known to induce their protection through the induction of antibodies. An antibody is a protein that is made by a cell type called the B cell, or B lymphocyte. Specifically, the antibody is the secreted form of the B cell receptor, or immunoglobulin. Antibodies are broadly classified into 5 groups called isotypes: IgM, IgD, IgA, IgE, and IgG. Each of these have different functions. IgM are produced very early on in infection and can help in particular to recognize sugars and play roles in complement activation (more on that shortly). IgD antibodies are made immediately after IgM and no one is certain what they do. IgA antibodies are antibodies at the mucosal surfaces (the parts of the body which are covered in a mucous membrane- anything continuous with the outside world including the digestive tract, respiratory tract, genitourinary tract, etc.) and help to serve a barrier function. IgE antibodies are the major antibodies produced against parasitic infections, but can also play a role in allergic disease. IgG antibodies are the major antibodies we generally care about when trying to see if someone is protected, which are associated with mature immune responses. It is estimated that each person can make approximately 1012 (about a trillion) distinct antibodies. In general, antibodies are very powerful defenses against infection for 3 things they do. The first is neutralization, which can mean one of two things. Many bacteria, like those that cause tetanus and diphtheria, cause disease by generating toxins that damage our body. Antibodies can bind these before they reach their target sites to cause disease. For viruses, antibodies can bind them before they can enter our cells and cause disease. Antibodies can also perform a function called opsonization. They bind a target and they mark it for destruction by recruiting the cellular actors of the immune system, like macrophages. Some antibodies (certain IgG and IgM for the most part) are also capable of complement activation. Complement refers to proteins in the blood, most of which are made in the liver, which are part of the innate immune system that serve to provide a general mechanism of defense. They are manufactured in an inactive form initially, but on activation, can have very potent antimicrobial effects. For example, complement proteins can form a structure called the membrane attack complex which makes a pore inside the cell it lodges itself in, killing it, which is very useful for dealing with certain bacteria. More recently, findings have also started to emerge which suggest that antibodies can destroy viruses after they have already entered our cells, but more data are needed to understand the significance of this.

What are antigens?

Strictly speaking, immunologists can get a bit careless with the nomenclature here. Formally, an antigen is anything that can be recognized by the immune system. Generally, when discussing vaccines or infectious disease, the more proper term is “immunogen” which denotes those antigens which produce immune responses (as we know not all of them do, for instance, self-antigens are not supposed to cause immune responses). The term “antigen” also has a lot of vagueness loaded into it. An antigen can mean an entire bacterium e.g. Bordetella pertussis, or a single protein or sugar on it, or even a specific region on the protein or sugar (this is known as an epitope). When discussing vaccines and the load on the immune system, the pertinent consideration however, is the number of antigens, and generally when we count these, we are referring to the discrete proteins and sugars in vaccines that are each capable of producing an immune response. Many parents voice concerns about how the vaccine schedule has seemingly grown over time, but this is actually not entirely true. In the past, we used a killed whole pertussis vaccine which contained entire dead pertussis bacteria. However, many unpleasant side effects resulted, or as vaccinologists say, it was highly reactogenic (primarily kids got very high fevers; it was still a safe vaccine but there were some headaches to deal with). As far as the number of distinct proteins and sugars, the whole cell vaccine contained several thousand. When it was noted that the immune system seemingly only cared about a few of them, the acellular vaccine was created which contained only those proteins and sugars which were important to the immune response, bringing the total down to 2-5 (depending on the specific vaccine used). CHOP has an explicit count of how many antigens are currently on the vaccine schedule, but the point is: over time, we have been able to protect against more disease with fewer antigens. The immune system generates responses against antigens in vaccines in accordance with the framework of the danger model and self vs. non-self models discussed above.

What are adjuvants and why are they needed?

There are a number of options for the kinds of vaccines we can make. For example, live vaccines tend to be extremely effective and they involve taking the pathogen (the agent that causes disease) and growing it for many generations in conditions not resembling physiological ones, like at temperatures below those that would occur in people. That causes the pathogen to adapt to those conditions, but adaptations are context specific, and they make the pathogen very poor at replicating under physiological conditions, thus unable to cause disease (with the exception of severely immunocompromised individuals). Inactivated vaccines refer to those which contain whole pathogens that have no ability to replicate i.e. they are dead. Both of these vaccine types contain PAMPs and thus they do not require adjuvants. Adjuvants serve to supply the immune system with necessary danger signals to produce an immune response. For example, some vaccines, like the hepatitis B vaccine, contain isolated antigens (proteins or sugars) which we want to direct a response against, but they have no pathogen. Ordinarily, the immune system would not respond to these. Actually, in one study (Dhodapkar, M.V. et al. (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233–238), dendritic cells (one of the types of cells of the immune system that presents antigens) were taken out of patients’ bodies and given proteins from influenza and then the cells were returned to the patients. This actually caused a suppressed response against influenza- the immune system was made to tolerate the proteins, in a manner similar to them being self. Hence, for these types of vaccines, called subunit vaccines, adjuvants are necessary for protection.

Vaccines whose antigens lack PAMPs require help to generate protective immunity (i.e. subunit vaccines which contain isolated antigens). This is where adjuvants come in. Adjuvants supply the immune system with danger signals needed for it to respond to those antigens, which it might otherwise ignore and then have to deal with for the first time when it encountered them in the context of that infection, or worse yet, tolerate. This is very well-illustrated with Hepatitis B vaccines. Hepatitis B vaccines contain one protein: the hepatitis B surface antigen, also called Australia antigen. By itself, this protein cannot interest the immune system as a threat. If, however, supplied with an aluminum-based adjuvant, it produces an excellent level of protective antibodies.

Can neonates and infants handle vaccines immunologically?

Unless the child is born very premature, the immune system they are born with is functional and has all the components it needs to generate immune responses. But, the immune system of a newborn is somewhat immature. Even though it responds to vaccines and can generate memory cells, it has difficulty holding onto immunological memory. For this reason, some vaccines require many doses before they can reliably protect the child. However, as stated earlier, everyone is capable of making approximately a trillion distinct antibodies. There is no reason that vaccines should be too much for a very young immune system to handle- they are after all designed for the very young in many cases and have to demonstrate efficacy in them before they ever get routine use.

If the immune system of the very young can handle vaccines so well, why can’t it handle natural infections?

This is a reasonable question based on the previous response. To understand this, it’s critical to understand first the consequences of pregnancy on the fetal immune system. The first cells of the immune system arise very early in gestation- as early as the third or fourth week- and the immune system of the fetus keeps developing throughout the pregnancy. However, from the perspective of the fetus and its mother, each is like a transplanted organ. Normally, unless from someone genetically identical (and mothers and their fetuses are not), for a transplant to be effective, the patient must receive significant immunosuppression, and even then, the organs won’t last forever. To deal with this problem, we have evolved a few key adaptations. The placenta is a critical one in that it acts as a barrier between maternal and fetal tissues and has cells at the interface which help to maintain a state of tolerance. But, the placenta is an imperfect barrier. It has to be: the fetus has to be able to exchange nutrients and waste across it. So the fetus has to undergo changes in its immune system to prevent rejecting its mother. Broadly speaking, its immune system becomes polarized towards immunological tolerance rather than clearing an offending antigen. Additionally, one cell type in particular is very important for the immune response and it does not arise until very late in gestation: the neutrophil. Neutrophils are part of the innate immune system and are the most abundant white blood cells. They are critical for defense against extracellular bacteria. Normally, neutrophils are recruited out of the bone marrow when inflammation occurs, but because they arise so late in gestation, the reserve that newborns have in their bone marrow is smaller. Additionally, the neutrophils demonstrate functional immaturity- they cannot yet effectively produce the chemicals they need to kill bacteria (reactive oxygen species). Thus, newborns are uniquely vulnerable to infection. They do have an immune system that is functional, but it isn’t fully developed. It needs training. It needs to learn to walk and then eventually run. Vaccines help to ensure that it gets that training.

Can you cultivate a strong immune system by repeated exposure to germs and refraining from handwashing?

This is a very bad idea for a number of reasons. I believe that when people propose to do this, they are bastardizing an interpretation of the hygiene hypothesis, which suggests that there is overall very little allergic disease in low income nations while a great deal in high income nations, and this is explainable by early childhood exposure to ubiquitous infections that would instruct the immune system for how it should respond to future infections. The press gave this idea a lot of coverage, but the reality is that there are problems with this idea which popular press have largely ignored. Firstly, there are genetic factors at play. Some people have a very strong genetic predisposition towards allergic disease (called atopy) and that is largely not modifiable, unfortunately. For another thing, we have known for essentially since the idea that has existed that the key difference in the infections encountered among nations stratified by income is likely infection by helminths- parasites. The issue is, the immune response to helminths is of the same nature as the overreaction the immune system has in allergy (Th2-driven) and some autoimmune diseases. Yet helminth exposure appears to be protective against allergic disease. Furthermore, certain autoimmune diseases and inflammatory bowel disease are also more prevalent in high income nations, despite being of the “opposite” type (Th1-driven) (Th1 and Th2 are not the only types of responses that the immune system can produce and it does get very granular, hence why calling them opposite isn’t entirely appropriate, but I use it here for simplicity’s sake). This was reconciled by an updated formulation of the hypothesis that essentially said that the host, in response to these helminths also produces cells that regulate the immune system and suppress responses, including the pathologic ones. Today though, most immunologists don’t really accept the hygiene hypothesis. Instead we have the Old Friends hypothesis. As mentioned earlier, your immune system has complex interactions with your commensal microbiota- they aren’t ignored. The Old Friends hypothesis says that humans coevolved with a number of other species and were exposed to their microbes. But in higher income nations these exposures are less frequent. This is supported by a number of observations, like how having a pet early in life can seemingly protect against allergic diseases in children. In short, the rise of allergic and autoimmune diseases seems to be related to lifestyle changes and a failure of the immune system to regulate itself. When people use the term “strong immune system” they seemingly refer to an invulnerability to infection, but the reality is an immune system that is too strong causes problems- it leads to autoimmune disease and allergic disease. What’s more, per the Old Friends hypothesis, it really isn’t about hygiene. The other piece to this of course, is the nature of the microbes in question. Our microbiota is colonized by commensal species- they eat at the same table (that’s what commensal means). They can have really important functions in our health too- for example, making vitamin K. But not all species are commensals, and furthermore, what is and isn’t commensal is context-dependent. Opportunistic infections occur when something which is commensal in one part of the body ends up somewhere where it behaves pathogenically. For example, staphylococcus and streptococcus species are found all over the skin, but can cause huge problems if they end up in the respiratory tract. If you’ve ever had a UTI, odds are it was E. coli’s fault, but E. coli is a commensal in the gut which everyone has. At the same time, some species are decidedly not commensal and have to cause disease to propagate and survive. This is perhaps best illustrated with tuberculosis. Tuberculosis is an obligate pathogen which causes a wide spectrum of disease, but in particular, it aims to cause disease in the lungs because it can only spread from person to person as pulmonary tuberculosis, though it has other manifestations. What’s more, microbes can pick up virulence factors from each other and evolve far more quickly than we do. For example, meningococcal bacteria can make an enzyme that destroys antibodies (incidentally, they are a commensal species in some people, and we don’t really understand why they sometimes “go bad.”). Additionally, we need to be cognizant that microbes evolve much more quickly than we do. Their generation times are much shorter. Their genomes are much smaller. And their genomes are also much more promiscuous. It’s not an accident that in the era before antibiotics and vaccines death by infectious disease was far more common and happened far earlier in life. And there’s very little evolutionary distance between the humans of today and those from even a few centuries ago. Repeatedly challenging yourself with pathogenic species is, in all likelihood, ultimately going to result in a pathogen that has evolved methods to get around all the immunological tools you have produced against it. You will not find an immunologist on the planet who will tell you not to wash your hands because it will give you a stronger immune system. But you may want to consider getting a furry friend. For your immune system.

How well equipped are we to evaluate the risks of vaccination (as opposed to non-vaccination) fairly?

The short answer is… not well. And this holds true across our entire species. The reason for this has to do a lot with cognitive biases and fallacies in our reasoning that are extremely prevalent. Risk evaluation ultimately comes down to a matter of math. We, ideally, use statistics for each option to judge which one is less risky. While the specific risk factors for person-to-person may vary, the statistics are what they are, which some people seem desperate to ignore. The evidence we have suggests that people really struggle with this. One study asked parents to complete a survey which asked the following:
“Imagine that, in the state you live in, there had been several epidemics of a certain kind of flu, which can be fatal to children under 3.

A vaccine for this kind of flu has been developed and tested. The vaccine eliminates the chance of getting the flu. The vaccine, however, might cause temporary side effects that are also sometimes fatal. The children who die from the side effects of the vaccination are not necessarily the same ones who would die from the flu. Except for these effects, neither the vaccine nor the flu has any long-term effects. Out of every 10,000 children under 3 who are not vaccinated, 10 will die from the flu. This rate applies equally to all groups of children, regardless of their prior health. Suppose that the overall death rate for vaccinated children were 5 out of 10,000. This rate applies equally to all groups of children, regardless of their prior health. Would you vaccinate your child?”

After this, the survey asked parents the following:

“If you answered “yes”: how high would the death rate for vaccinated children have to be in order for you to change your mind? (This number should be greater than 5 out of 10,000. Remember that the death rate for unvaccinated children is 10 out of 10,000.)”

“If you answered “no”: how low would the death rate for vaccinated children have to be in order for you to change your mind? (This number should be less than 5 out of 10,000. If you would not vaccinate under any circumstances, use 0.)”

How did parents respond?

The mean tolerable risk of the vaccine in the hypothetical vignette among the vaccinators was 5.4 deaths per 10,000, and among the nonvaccinators it was 2.4 deaths per 10,000 (p < 0.001).

In other words, for parents to agree to vaccinate their child, the risk of not vaccinating had to be more than twice as high as the risk for vaccinating. How can that be? This is a concept known as omission bias. It basically says that where we are uncertain about how to proceed, we have a tendency to elect to do nothing and let events take their course, for fear of choosing wrongly. Parents often report that they would feel less guilty if something bad happened if they didn’t vaccinate than if they did, as if they did that was a choice they made. However, not making a choice is still a choice. Our choices have time limits. Eventually, by choosing not to act, the decision is taken out of our hands, and ultimately, we are the ones who chose to make it that way. In a similar vein, some anti-vaccinators argue that you can’t take back a vaccine. But you can’t take back a vaccine-preventable disease either. One study noted that vaccine refusal was associated with 35 times more risk of getting measles and 22 times greater risk of getting pertussis. Hence, vaccination is clearly more than twice as safe as non-vaccination as far as the risk of vaccine-preventable diseases.

Similarly, parents also encounter many terrifying anecdotes on the internet, most of which are obviously recognizable as false to someone with significant medical training or understanding of vaccines but are nonetheless very difficult to shake even after one explains these things. Why is that? That’s something called negativity bias. Consider the following scenario: suppose you have a car that is many decades old, well past its warranty. Now suppose you have to get to work and you get in the car and it starts without issue. You don’t invest much mental effort into thinking what went right there. You expect it to work, and it does. Except- now suppose it doesn’t start. Logically this is the probable outcome, isn’t it? It’s an old car. They aren’t designed to last forever. But now suddenly you have to know why. You start picking it apart, attempting to run diagnostics- even though you may have no experience as an auto mechanic. The point of this is to show that we invest far more effort into thinking about when things go wrong than when they go right. The significance of this in vaccination is twofold. Firstly, it makes it so that people don’t really hear about what happens most of the time with vaccines: nothing exciting. The reality is that the vast supramajority of vaccinations are completely uneventful. But those aren’t interesting and you don’t hear about them. The second thing is it makes those vanishingly rare instances where something bad does happen all the more salient in our minds. This also skews our perceptions.

Furthermore, we all have a tendency towards a phenomenon known as confirmation bias. In essence, confirmation bias is the tendency of us to constantly gather findings that agree with our preconceived ideas about how the world works and reject those which go against them. If you believe that vaccines are harmful and you are given evidence to the contrary, you will typically unconsciously gather findings that continue to support that and reject those which go against it. Similarly, if you support vaccination, you are much more likely to reject information which speaks about the harms of vaccines. Of course, evidence unequivocally supports vaccination as a practice- but it’s important to analyze all data critically. Much of this happens in an unconscious manner, however. For example, suppose a parent reads a heartrending account about a child who developed acute disseminating encephalomyelitis (ADEM) following vaccination. Some might stop there. But some might want to learn more, as the plural of “anecdote” is not “data.” What do they do? Typically they turn to the internet. From there the questions abound: “Do vaccines cause ADEM?” “vaccines cause ADEM” “How do vaccines cause ADEM?” These all sound like innocent and reasonable questions but in a subtle way they are poisoning the well of the results the search engine will generate. The way these queries are phrased is much more likely to give confirmatory results than disconfirmatory ones. Relatively few people on the other hand would go to pubmed to limit the search to indexed publications. Of those, fewer might try to phrase the query neutrally with Boolean operators like ““vaccines” AND “ADEM”.” Fewer still would filter by study type to exclude opinions, letters, case reports, and studies performed in non-human species. A smaller proportion of those may try to construct a search query using advanced search or MeSH terms.

Research is hard (understatement of the eternity). It takes decades to approach something resembling mastery. Searching for the right literature is only a tiny part of that. Critiquing that literature, understanding strengths, weaknesses, limitations, and which questions it doesn’t answer, takes far longer to master. And it’s not a reasonable thing to ask a parent without professional scientific training to do. There is absolutely nothing wrong with having questions and if you find something that is personally concerning to you, you should ask an expert. Talk to your pediatrician. They have experience evaluating these studies and understanding strengths and weaknesses.

Are vaccines victims of their own success?

Without question. It would not be reasonable to accept risks without a possible benefit. But when that benefit is so abstract, it may as well not exist. The reality is, vaccines have been so successful at bringing down the incidence of diseases they prevent that we hardly ever see them anymore. Polio once put entire generations of people in iron lungs and stole their ability to walk. Rubella disfigured infants for life and left them with profound cognitive and mental disability. Diphtheria was the strangling angel of children. Tetanus locked people in opisthotonos until they died. A detailed account of pertussis is provided in the video, but you can see what it looks like in its paroxysmal phase here: https://www.youtube.com/watch?v=S3oZrMGDMMw. In short, vaccines have managed to completely eliminate some diseases from the US and other high-income nations: diphtheria, polio, rubella, smallpox, measles. With some other diseases we’re getting close. But the thing is: these diseases haven’t gone anywhere. They’re no more than a plane ride away. I think COVID-19 illustrates how easily a disease can spread when there isn’t uptake of a preventive vaccine. Having never seen these diseases, having no understanding of how devastating they truly are, how can we accurately hold the risks and benefits in our heads?

But what about Natural Immunity?

Firstly, a note: the term “natural immunity,” needs to be retured. The proper terminology is “disease-acquired immunity” or “infection-acquired immunity.” Here is why:

Another fallacy that can cloud our thinking is the naturalistic fallacy. There is a perception that vaccines are unnatural and therefore bad. The best explanation for why this is erroneous is simply that the concept of “natural” makes no sense. Presumably, natural means created by nature, i.e. not artificial. But consider this: let’s suppose I have tomato paste. This is a reasonably natural product, most would agree. It is simply crushed up tomato. But now let’s suppose I add sugar to it. Many would contend this is now less natural. That doesn’t make very much sense though- sugar is plenty natural. It comes from plants which harvest the energy from the sun to make it. But nonetheless, people will claim it less natural because a human intervened to add that sugar. Let’s now suppose I take this tomato paste, and I remove all this added sugar. It is now equivalent on a chemical level to the sugar-free paste I started with originally. So it’s more natural right? But I, a human, had to intervene twice to make it. In other words, I made something more natural. Which directly contradicts how most people think about the term “natural.” In other words- this concept has no logical consistency, which means it’s a poor metric to base decisions on. Nonetheless, natural has certain connotations. People think of it as indicating greater purity, a moral value of some kind. But the reality is that how natural a substance is has absolutely no bearing on how dangerous it can be.

It’s true that there are some advantages that infections have over vaccines as far as the protection they create from the immune system, but there is no case in which they outweigh the profound disadvantages. For example, for some infections, immunity lasts longer than that which is conferred by the vaccine. Except- this isn’t always the case. For instance, HPV vaccines seem to provide much more durable protection than infection does, with none of the cancer risks. And immunity to measles via MMR vaccine appears to be about as good as for the infection, but it’s far safer. This is worth examining by looking towards a few specific diseases. Specifically, the ones where people question why there may be a vaccine at all.

Forcing a child to suffer through a disease that we have every means to prevent by withholding preventive care from them does not confer a rite of passage unto them. It is abusive.

Natural Immunity to Hepatitis B: why a birth dose?

A persistent talking point for the antivaccine lobby is why we should do the hepatitis B vaccine within 24 hours of birth. Usually this is framed not as a genuine concern over the safety of doing this but rather by stigmatizing hepatitis B as a disease of sin, something that only sex workers or drug abusers can get. Foremost, it is critical to address this: injecting a moral valency into a disease is immoral. There are no “good” diseases. No one DESERVES disease. Disease is the evil that we should all be fighting. With hepatitis B, this is no different. Hepatitis B is a bloodborne pathogen, and it is the leading cause of liver cancer globally and a critical cause of liver cirrhosis, which eventually becomes fatal. Therapies for hepatitis B are expensive and brutal. It’s true that certain individuals are at higher risk but it’s not as simple as limiting vaccination to them. Hepatitis B infection can have an extremely long incubation period, and as many as 90% of people globally who have hepatitis B are unaware of it. Furthermore, hepatitis B can remain functional outside the body for over a week, some estimates even reporting a month. Exposure is much easier than one might assume and children aren’t careful about where they put their hands or how they handle sharp objects. Hepatitis B can have an acute and a chronic form. 40% of those who develop acute hepatitis B will be sick enough to require hospitalization. In some individuals, hepatitis B progresses into a chronic form, which is the major risk for cirrhosis and hepatic adenocarcinoma (liver cancer). If acquired in infancy, there is a greater than 90% chance of progression to the chronic form. What’s more is that hepatitis B screening is imperfect and can miss infection in pregnant women who can go on to transmit the infection vertically to their child. Ultimately, by far the safest option is to immunize infants with hepatitis B vaccines within 24 hours of birth. To refuse to do this is to make a choice for your child that could very well cost them their life or quality of life.

Why do we need a varicella vaccine?

Varicella, which you may know as chickenpox, is usually a vaccine which many parents feel is unnecessary. It is after all, “just chickenpox.” But, what does that mean really? It’s true that in most people varicella primary infection manifests as a fever and a rash and is typically self-limiting. However, people seem very hasty to ignore what happens after the varicella infection. Firstly, about 1 in 3 people who have varicella infections will develop shingles, or zoster. Shingles is a debilitating pain condition that occurs when varicella zoster virus reactivates inside the neurons. Varicella zoster is a herpesvirus, which persist permanently inside infected cells as a segment of DNA called an episome, and can lie dormant for years. But, should the immune system become suppressed, such as from stress, sleep deprivation, a course of steroids, or even just aging, reactivation can occur. The pain from this is absolutely debilitating. This also ignores the possible complications from varicella. People often have a very binary perception of disease as far as how dangerous it is. Either you’re likely to die or you’re not. But it’s not that simple. It’s true that death from chickenpox is quite rare. But what about chronic pain that makes you wish you were dead? It is possible for varicella zoster to cause a condition colloquially known as suicide disease by infecting the trigeminal nerve. The condition is so named because the pain is so horrible that it has been known to drive people to suicide. In some individuals, the pain from a shingles outbreak does not resolve so easily, instead causing a condition called postherpetic neuralgia, which is essentially scarring of the nerves and causes pain for months to years. In a sense though, that’s the tip of the iceberg. Most people will generally accept that shingles is terrible but few consider chickenpox to be as threatening. Chickenpox is one of the few conditions known to cause strokes (cerebrovascular accidents) in children (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912415/pdf/nihms776193.pdf). And if that isn’t enough there’s one thing everyone knows about chickenpox: it’s really itchy. That doesn’t sound like a big deal except chickenpox leads to a number of bacterial superinfections through the skin which can be devastating, like staphylococcal scalded skin syndrome. It can also cause pneumonia, meningitis, transverse myelitis (inflammation of both sides of a section of the spinal cord typically resulting in paralysis, potentially loss of bowel and bladder control, and loss of sensation), glomerulonephritis (inflammation in the kidneys), myocarditis (inflammation of the heart muscle), and purpura fulminans (a very dangerous clotting abnormality which causes characteristic bruising and internal bleeding with skin necrosis). By contrast, the vaccine can produce a mild rash in about 5% of recipients, and cases of shingles from it are very rare. The vaccine is also very effective with > 90% mounting protective antibody levels which last at least 6 years.

Why do we need a measles vaccine?

Ah yes, another one of those “fever and a rash” diseases. Measles however, was once one of the greatest public health threats imaginable, accounting for as many as 4 million deaths each year before we had a vaccine. Case fatality ratios for measles are about 1 to 3 per thousand in higher income nations but can be as high as 4 to 10%. This however is not the whole picture. About 1 in 3 measles patients will experience some sort of complication. The most common of these is diarrhea but measles is also a key cause of pneumonia and encephalitis. Pneumonia is the most common cause of death from measles but the encephalitides it can cause are particularly dangerous. In particular, subacute sclerosing panencephalitis is a condition caused by measles that manifests years after initial infection starting out very subtly: personality changes or worsening school performance, eventually progressing into coma and death. Individuals who develop SSPE have a >95% chance of death, some sources even reporting that all cases are fatal. Infants are at particularly high risk, with 1 in 600 getting the complication from measles. The general risk is about 1 in 10,000. These may sound like small numbers, but consider that measles is the most communicable human disease known, and we have no way of knowing whether or not an individual will get these conditions. On top of this, measles causes profound immunosuppression which can last for a period of years following initial infection. This has been compared with having a case of HIV for 5-10 years untreated. One study noted that after measles infection, patients could have over 70% of their antibody repertoire eliminated. This leaves them vulnerable to other infections, including those which they may have encountered before which is known as immunological amnesia. There are also recorded instances of measles causing appendicitis, myocarditis, pericarditis (inflammation of the sac around the heart), thrombotic thrombocytopenic purpura (a bleeding disorder; this occurs so commonly that there aren’t precise data on its incidence), hepatitis, ileocolitis, glomerulonephritis, cervicitis, etc. Measles is also more dangerous in pregnant people and if acquired congenitally can have a 32% case fatality ratio. Treatment options are limited. There is no antiviral therapy for measles. Vitamin A supplementation is useful when the individual has vitamin A deficiency, but this is not a common occurrence in high income nations (it may also have value if the child is under age 2 but no mortality benefit has been demonstrated otherwise). This is not the portrait of a mild, self-limiting illness like the anti-vaccine lobby may have you believe. This is a genuine public health threat. It is inarguable that the measles vaccine has saved millions of lives. As for the vaccine, there is a small risk of immune thrombocytopenic purpura (approximately 1 in 30,000 cases and much less than for measles infection; this is generally a self-limiting consequence and does not require intervention), a 1 in 3 million risk of encephalitis (the risk of some kind of encephalitis for measles is about 1 in 1000), a small risk of febrile seizure (about 1 in 3000; febrile seizures are not like epileptic seizures. They are benign and do not indicate brain damage and occur from any substantial temperature change in very young children. They do not indicate a heightened risk for epilepsy. You can read more here: https://www.healthychildren.org/English/health-issues/conditions/head-neck-nervous-system/Pages/Febrile-Seizures.aspx), pain and swelling at the injection site, etc. The risks posed by measles are far, far greater.

Why is there aluminum in vaccines?

Firstly- aluminum is not a heavy metal. The term heavy metal actually has no meaning. It is an overt attempt to emotionally manipulate people with charged language suggestive of a toxic risk. Some vaccines require help to work properly and produce antibodies. Aluminum-based adjuvants are salts of the aluminum ion which help to promote high levels of antibodies following vaccination. Over the years, many concerns have been raised by various actors about the safety of aluminum-based adjuvants. For context, these adjuvants have been in use for nearly a century now without any significant safety concerns noted despite extensive pharmacovigilance networks for vaccines. However, there are simple rebuttals to these concerns. Firstly, the concern that aluminum causes allergies. This is usually based on an observation that aluminum-based adjuvants promote the production of IgE which is pathogenic in allergic disease. However, people generally stop there, ignoring a key fact: everyone makes IgE, but not all IgE leads to allergy. In truth, high affinity IgE leads to allergic disease but low affinity does not, and these are produced through different pathways and are distinct. The best rebuttal however comes from the fact that aluminum-based adjuvants (the very same ones as in vaccines) are used to treat allergic disease in subcutaneous immunotherapy (SCIT). The patient is challenged with progressively escalating doses of their allergen and the aluminum-based adjuvant. SCIT is considered the gold standard for allergy immunotherapy. It therefore makes no sense that aluminum could cause allergic disease. Then there’s the matter of whether or not aluminum can cause autoimmune disease. There are very rare circumstances in which vaccines could cause autoimmune disease, and in particular certain older vaccines were known for this (e.g. the first rabies vaccines). However, a large cohort study examining the effect of SCIT with aluminum-based adjuvants compared with conventional allergen therapy compared the incidence of autoimmune disease in those receiving SCIT and those getting conventional allergen therapy: the burden of autoimmune disease in patients receiving SCIT was LOWER than in those who did not receive it. Furthermore, on the level of immunological principles this does not make very much sense. Even if you made a cell that could react against self-antigen, there are tolerance mechanisms that would terminate that immune response because of the tissue damage it causes. Additionally, infections are known to be especially significant as causes of autoimmune diseases. For example, we know that rotavirus infection can seemingly cause type 1 diabetes, and recent findings show that completion of the vaccine series reduces this risk (though these vaccines do not contain aluminum-based adjuvants): https://www.nature.com/articles/s41598-019-44193-4.pdf. The ideas about aluminum also become quite self-defeating when you take into account how prevalent aluminum is. It is everywhere. It is in the food you eat, the air you breathe, breastmilk, formula etc. It is the third-most abundant element in the Earth’s crust. There is actually no correlation between the aluminum content in hair and blood and a child’s vaccination history. The aluminum in vaccines does not represent any significant burden as far as toxicity. In fact, aluminum toxicity itself is extremely rare. It is essentially limited to patients who have severe kidney disease and require dialysis or those who work in aluminum mines (and even then, some evidence suggests that that is the fault of dust exposure rather than the aluminum). In general, the kidneys are extremely good at clearing aluminum from the body (which is why clear instances of disease are basically limited to dialysis patients who received the aluminum intravenously in their dialysate fluid). Furthermore, when considering the absorption of aluminum through different routes of administration, the pertinent consideration is bioavailability- the proportion of the aluminum which ends up in the blood stream. Vaccines containing aluminum-based adjuvants are given intramuscularly, and contrary to popular belief, this is NOT the same as injecting it into the blood stream (that would be intravenous injection, like the dialysis patients). When injected intravenously, regardless of the substance, all of it ends up directly in the blood, so it is 100% bioavailable. Intramuscular aluminum is released very slowly into the blood, at a rate of about 0.6% of the entire deposit per day. By contrast, about 0.3% of the aluminum in our gut ends up absorbed via our diet, but there is so much more contributed via diet than vaccines that this ends up being far more aluminum in the blood. There is no toxicity risk here. Aluminum in vaccines is extremely safe and necessary. Edward wrote in detail about aluminum here: https://medium.com/@edwardnirenberg/in-defense-of-aluminum-based-vaccine-adjuvants-much-ado-about-nothing-633151d35c30?source=friends_link&sk=5571f1e921a03d022d1bdbf06f42518e

Why is there formaldehyde in vaccines?

Formaldehyde has a reputation as a dangerous and carcinogenic molecule, and while that isn’t unwarranted, it would constitute a grave mistake to extrapolate that to vaccines. Firstly: we all make formaldehyde. It’s part of our metabolism and we shunt it into biochemical pathways to make nucleotides (the precursors to DNA and RNA) and amino acids (the precursors to proteins). Formaldehyde in an infant is present in concentrations about 100 times greater than in any vaccine, and the formaldehyde from a vaccine can be metabolized in a matter of minutes. What’s more, formaldehyde can also be a critical reason why some vaccines are safe. At the molecular level, formaldehyde behaves like glue. When making tetanus vaccines, the toxin from the bacteria, tetanospasmin, is treated in a solution of formaldehyde and lysine. Tetanospasmin is an enzyme that can digest proteins in our neurons which are required to release inhibitory neurotransmitters that suppress muscle contraction. But, the enzyme has to able to move around to accomplish this. The formaldehyde blocks this from happening by sticking it together so that it can’t. At the same time, the enzyme retains its shape so that antibodies on the immune system can recognize both it and the actual toxin if you become exposed. Regarding the carcinogenicity of formaldehyde, we need to discuss chemistry again. There are a few different types of carcinogens, but in general, they all have to be able to change DNA. There are a few ways of going about this, but the strategy formaldehyde uses is very inefficient. Formaldehyde is an extremely reactive molecule, and it can react with the nucleotides in your DNA to change them. However, it is very difficult to cause cancer in this way. The DNA in a cell is locked away inside a nuclear envelope deep inside the cell. For formaldehyde to reach it, it would have to make it past a huge number of molecules, unchanged, and react specifically with DNA, and formaldehyde is extremely reactive. This is a very challenging thing for formaldehyde to accomplish, chemically speaking. Hence, in general, the development of cancer from formaldehyde exposure requires frequent, high doses, at levels far beyond what is achievable by vaccines.

Why is there thimerosal in vaccines?

With the exception of the multi-dose flu vaccines, there is no thimerosal in vaccines. Thimerosal is a molecule that dissociates into ethylmercury (a mercury atom with an ethyl group- 2 carbons with 5 hydrogens). Ethylmercury is not the dangerous kind of mercury. That honor goes to methylmercury (mercury with a methyl group- 1 carbon bonded to 3 hydrogens) or possibly inorganic mercury. The reason for this is that the two have very different pharmacokinetics- the body treats them very differently. Methylmercury can be dangerous because it can build up to toxic levels because the body is slow to clear it. Talking about the hazards of vaccine components however is pointless without explaining why they are there in the first place. Thimerosal is a preservative that protects vaccine vials from contamination. Several crucial historical incidents explain its necessity, well documented from Paul Offit’s Autism’s False Prophets. He writes:

“Between 1900 and 1930, companies packaged vaccines almost exclusively in multidose vials, with a typical vial containing ten doses. Because a large percentage of the cost of vaccines is determined by its packaging—sterile glass vials, rubber stoppers, metal tops, and labels—as well as the labor required to fill each vial, multidose vials allowed vaccines to be made much less expensively. Doctors kept these vials in refrigerators in their offices, often for months at a time. To give a vaccine, they would insert a needle through the rubber stopper, pull the liquid up into a syringe, and inject it. Unfortunately, by constantly violating the rubber stopper with a needle, doctors and nurses occasionally contaminated the vial with bacteria. In 1916, in Columbia, South Carolina, a batch of typhoid vaccine contaminated with bacteria caused seventy severe reactions and four deaths. And in Queensland, Australia, in 1928, twelve children injected with a contaminated diphtheria vaccine died from bacterial abscesses and bloodstream infections. By the 1940s, most multidose vials of vaccines contained preservatives to prevent contamination…

“They found that thimerosal was much better at killing bacteria than other antiseptics. They also found that they could inject hundreds of milligrams of it into rabbits and rats without any harmful effect. Then they gave it to people. In 1929, during an outbreak of bacterial meningitis in Indiana, Lilly scientists gave thimerosal to doctors to treat the infection. It didn’t work. (It would be another six years before the first antibiotic, sulfa, entered the United States.) Although thimerosal didn’t treat meningitis, doctors found that it was safe. Adults injected with 2 million micrograms of thimerosal didn’t suffer symptoms of mercury poisoning; the amount was 10,000 times greater than the FDA later found babies had received in vaccines.”

Offit, Paul. Autism’s False Prophets (p. 62). Columbia University Press. Kindle Edition.

Of note, one possible interpretation of the failure to cause meningitis is that the thimerosal could not effectively enter or be retained by the central nervous system which further makes concerns about neurotoxicity untenable. Thimerosal was also thought to cause autism by some individuals as a form of mercury toxicity and this is nonsensical for several reasons. The most important is that there is no correlation between vaccinations and autism. Beyond that however, mercury toxicity has no resemblance to autism whatsoever. A detailed discussion of that can be found in the citations for thimerosal.

On chemophobia:

It is very common to hear sayings like “you should never put things in your body you can’t pronounce.” The reality is that almost every compound you can think of has a version of a name you can’t pronounce. For instance:

Ingredients of All-Natural Blueberries

The IUPAC assigns systematic names to common chemicals that we encounter every day because they are useful. If you know the systematic name of a compound you can deduce exactly what it looks like. Take for example, glucose. Glucose is a vital nutrient and the principal source of energy for our cells. The IUPAC systematic name for glucose is (2R,3S,4R,5R)-2,3,4,5,6-Pentahydroxyhexanal. In the same vein, it’s important to explain that there is a critical distinction between salts and their elements. A salt is simply a substance that is composed of positively and negatively charged ions- charged molecules. Sodium chloride is just table salt. You consume it every day (even if you don’t add salt to things it is in your food). Sodium metal however, is so reactive that we have to store it in mineral oil. If it has contact with water, it will explode. It also produces a very corrosive alkaline solution at the site where it reacts with the water. Chlorine was used as a chemical weapon in WWI. When it comes into contact with the water in your mucous membranes it makes hydrochloric acid and bleach. Neither sodium ions nor chloride ions have either of these properties. On the contrary, they are chemically (relatively) inert, and we need both for our survival. In short, everything you can interact with is a chemical, and how natural it is or what name it’s assigned has nothing to do with how safe or dangerous it is for you. Even very similar chemicals can behave very differently in our bodies. If you don’t know, ask an expert.

Sources

“What’s In A Vaccine?”

Sources

Antibodies:

Antigens:

Newborn Immune System:

Pregnancy:

Maternal immunization:

Not vaccinating leads to 20-30x increased risk at getting VPD’s like Pertussis:

Vaccines are a victim of their own success:

No action is still an action- still choosing either way (Omission Bias):

Certain vaccines are needed only for travel:

Confirmation bias- bias saliency:

Negativity Bias:

Natural Immunity/Naturalness Bias:

Pertussis:

Varicella:

Measles:

Hepatitis B:

Formaldehyde:

Aluminum-based adjuvants:

Thimerosal:

SARS-CoV-2/COVID-19: How can we tell whether a vaccine works?

mRNA Vaccines and COVID-19