Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines.
Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome.
MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition.
[P]oorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain.
This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity.
Particulate aluminum salts (known as alum) have been the main approved adjuvants for use in human vaccines for more than 80 years. They are currently used in vaccines against tetanus, hepatitis A, hepatitis B, human papillomavirus, haemophilus influenzae B, pneumococcal and meningococcal infections, and anthrax.
In spite of their long usage, the literature has pointed out that the adjuvanticity mechanisms of aluminum salts remain basically unknown despite most active investigation in the field in recent years.
In a recent evaluation of 583 patients collected from 1994 to 2012, the median time elapsed between the last alum administration and [biopsy detecting MMF illness] was 65 months [5.4 years]. Compared to our previous reports, this time had gradually increased from 36 months in 2001, i.e., shortly after the peak of French adult immunization, to 53 months in 2003.
In practice, we consider that the MMF is unusually persistent when time elapsed from last immunization to the MMF detection exceeds 18months. It is important to consider this point in young children who receive multiple vaccine injections in the first year of life, thus increasing the risk of coincidental association between a constitutive muscle disease and MMF detected in the quadriceps muscle used for pediatric immunizations.
Taken together, chronic muscle pain, chronic fatigue, and cognitive dysfunction are consistent with the so-called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and about 50% of MMF patients meet international criteria for ME/CFS.
The underlying cause of ME/CSF is currently unknown, but the illness is thought to be triggered by an abnormal immune response to an infectious or toxic agent, that results in chronic immune activation.
Aluminum has long been identified as a neurotoxic metal, affecting memory, cognition and psychomotor control, altering neurotransmission and synaptic activity, damaging the blood–brain barrier (BBB), exerting pro-oxidant effects, activating microglia and neuroinflammation, depressing the cerebral glucose metabolism and mitochondrial functions, interfering with transcriptional activity, and promoting beta-amyloid and neurofilament aggregation.
Alum has been used for decades to levels considered as an accept- able compromise between its role of adjuvant and its toxic effects by the industry and the regulatory agencies.
[T]he MMF story revealed several gaps in the knowledge on alum particles, including their exact mechanisms of action, their fate after injection, their systemic dissemination, and their safety on the long-term.
Efforts have been done in the last years to develop novel adjuvants, but attempts to seriously examine safety concerns raised by the bio-persistent character and brain accumulation of alum particles have not been made.