Answer by Tirumalai Kamala:
Why indeed? Accidental discovery plus expediency explains aluminum salts in vaccines. Accidental discovery of enhancement of immunity. Let’s also be accurate. Some, not all, vaccines have specific aluminum salts, not just any aluminum.
Aluminum Salts in Vaccines: The History
Some aluminum salts enhance circulating antibody titers
It starts with an accidental early 20th century discovery by . His team was trying to prepare pure versions of diphtheria toxoid and render it insoluble. The idea? Insoluble material might hang around longer at the site of injection (depot effect). This might induce a stronger immune response. They found certain aluminum salts easily precipitated diphtheria toxoid (1). So far so good. What happened when they injected the aluminum salt-precipitated diphtheria toxoid into guinea pigs? An immunological alchemy. Specifically, toxoid precipitated with aluminum potassium sulfate was consistently better in driving key aspects of immunity compared to toxoid alone .
1. Higher circulating antibody titers of anti-diphtheria antibodies.
2. Higher titers faster.
3. Longer lasting titers.
Eventually, others corroborated Glenny’s data that aluminum salts had this effect in different species with different antigens, antigens being protein molecules derived from or associated with disease-causing micro-organisms.
Tetanus toxoid? Similar results.
Rabbits and horses? Similar results.
Thus, the aluminum salt effect was generalizable. What effect precisely?Aluminum salt-adsorbed antigen stimulated stronger circulating antibody titers compared to the antigen alone. Today, we call such an effect .
Aluminum Salts in Vaccines. When they started and Why.
Spurred by Glenny’s data, confirmation by other scientists, and public health need for vaccines against diphtheria and tetanus, vaccine manufacturers started adding certain aluminum salts such as aluminum potassium sulfate in their vaccines, to great success. For example, New York City averaged 14000 diphtheria cases with 1290 deaths between 1910 and 1919, which dropped >97% to 300 cases with 10 deaths by 1942 to 1944, following aluminum salt-adjuvanted diphtheria toxoid vaccination (2). Eventually, aluminum potassium sulfate was phased out in favor of aluminum hydroxide and aluminum phosphate because they were easier to manufacture. Thus it came to be that some common vaccines such as DTaP (Diphtheria-Tetanus-acellular Pertussis) contain aluminum salts. Early in the 20th century, regulatory clearance for such vaccines was much easier.
1. At that time, these aluminum salts were considered safe or at least there were no large-scale, well-known studies in the scientific or medical literature suggesting otherwise.
2. It was a less well-developed and much less risk-averse regulatory landscape. Randomized clinical trials were still in the future. For example, to quote the CDC ( ), “Efficacy of the (tetanus) toxoid has never been studied in a vaccine trial.”
3. Direct human experimentation was still acceptable. Consider , for example.
Early public health success and safety record of such aluminum supplemented vaccines spurred its addition in newer vaccines such as Hepatitis A and B, and papilloma virus. As decades passed, billions of us around the world got an aluminum salt-containing vaccine at least once, most likely in childhood.
No problem, right? Not exactly, for a few reasons.
- Scientifically, we didn’t understand how aluminum salts enhance immunity against unrelated biological entities. In fact, study in this area was practically non-existent for many decades.
- We get vaccinated by the millions every year with aluminum-containing vaccines with little adverse effects*. As newer vaccines in the pipeline got approved, each jab of many approved vaccines’ added cumulatively to the amount of aluminum we got, something that was never considered separately as a risk factor**. Why? Complacency and inertia? We understand this phenomenon. We see it every day and practice it ourselves. The phenomenon of “If it ain’t broke, don’t fix it”. Here’s a physician’s well-articulated reasons ( ) why we need to plug this gap in our understanding.
Aluminum salts in vaccines: How do they enhance immunity?
For the longest time, Glenny’s disarmingly simple idea prevailed. Aluminum salts in vaccines created a vaccine depot at the site of injection. Over time, vaccine would release slowly from the depot triggering sustained immune responses. That’s it.
For 70 years or more, there was little or no systematic research into how aluminum salts actually enhanced immunity.
How do aluminum salts drive antibody responses? Research in this field really took off only in the past decade (2, 3). Some mouse models implicated the, a bunch of proteins important in getting the earliest stages of immune responses going while subsequent studies contradicted this. Others suggested they induced local damage through DNA or uric acid release from dying cells. Caveats of most of these studies? They didn’t use the same aluminum salts present in approved human vaccines, making them irrelevant for understanding how they work in us.
What about Glenny’s depot effect idea? Even that appears inaccurate, according to at least one mouse model study (4) which thankfully used an aluminum salt, aluminum hydroxide, also used in human vaccines.
Bottomline? We certainly know more then Glenny but we still don’t fully understand how aluminum salts enhance immunity (5).
Aluminum salts in vaccines: Is its enhancement of immunity a limitation?
For practical purposes, aluminum salts in vaccines are a one-trick pony. Good at enhancing circulating antibody titers but not much else. This is a serious limitation. Why?
Bloodstream spread of bacteria that induce self-limiting infection at their site of entry is dangerous if they spread through the blood to other sites like the brain. Circulating antibodies against them bind and stop them in their tracks to prevent such spread. Aluminum salts in vaccines help spur such antibodies.
However, circulating antibodies are not optimal for every situation. For example, CD8 T cells are often most effective against viruses yet aluminum salts are quite inefficient in spurring them. Such limitation in range of immunity is the key incentive driving research to identify newer adjuvants capable of promoting a broader range of immunity.
Aluminum salts in Vaccines: Which vaccines and what salts?
Some current aluminum-containing vaccines:
DTaP (Diphtheria-Tetanus-acellular Pertussis), HepA, B (Hepatitis A and B), Pneumococcal Conjugate vaccine
Aluminum used in current vaccines:
aluminum hydroxide, aluminum phosphate, alum (potassium aluminum sulfate)
Non-vaccine Aluminum Toxicity:
Today, aluminum is ubiquitous in our life, in the toothpaste we use to brush our teeth, the cookware we use to cook food, the salt we use in our food, our baby milk and infant formulas, aluminum foil, soda cans, and the deodorants we use on our body. Yet medicine has shown that aluminum can also be toxic, specifically in kidney disease and in pre-term infants.
Aluminum toxicity was first documented, not with vaccines, but in kidney disease dialysis patients in Newcastle, England in the 1970s (6, 7). Careful studies implicated aluminum in the dialysis. How? The bone disease these patients developed was reversed by depleting the aluminum in their dialysis fluid.
*Aluminum salts in Vaccines: Are they safe?
What’s the safety record for aluminum salt-containing vaccines? Reports in 1969 (8), 1980 (9) and 2004 (10) suggest an excellent safety record. There are several caveats to such a conclusion. Typically, aluminum salt-containing vaccines induce pain, swelling and redness at the injection site (11). Greater with subcutaneous, less with intramuscular injection (12, 13). Short-term symptoms such as pain, swelling and redness dissipate quickly, and may be unrelated to long-term effects. Here, cost is an important limitation. Longer the follow-up, more expensive the study.
Short-term effects other than pain, redness, swelling? Contact hypersensitivity (14) in one study.
Long-term effects? Association with sarcoma in sub-groups of cats (15, 16).
Other effects? Localized muscle weakness and fever associated condition called macrophagic myofasciitis in some children (17).
** What about the cumulative effect of aluminum salts associated with more vaccines, and more vaccine jabs? Systematic research on this issue is sparse. A recent study (18) mathematically estimates that aluminum concentration in blood from vaccines given in the first year of life is below the minimal level established by the US Agency for Toxic Substances and Disease Registry. A small study (19) in pre-term infants corroborated their model.
Our past suggests it’ll be years before we fully understand how aluminum salts stimulate immunity to vaccines and how safe they really are. One thing we can be sure of? We know we need better characterized adjuvants.
Immunological alchemy just won’t do in this day and age.
- Glenny AT, Pope CG, Waddington H, Wallace U. The antigenic value of toxoid precipitated by potassium alum. J. Pathol. Bacteriol. 29, 31-40 (1926).
- Leslie, Mitch. “Solution to vaccine mystery starts to crystallize.” Science 341.6141 (2013): 26-27.
- Alfrey, Allen C., Gary R. LeGendre, and William D. Kaehny. “The dialysis encephalopathy syndrome: possible aluminum intoxication.” New England Journal of Medicine 294.4 (1976)
- Edelman, Robert. “Vaccine adjuvants.” Review of Infectious Diseases 2.3 (1980): 370-383
- Lach, Boleslaw, and Edward J. Cupler. “Macrophagic myofasciitis in children is a localized reaction to vaccination.” Journal of child neurology 23.6 (2008): 614-619