Aluminium oxyhydroxide (alum), a nano-crystaline compound forming agglomerates, has been introduced in vaccine for its immunologic adjuvant effect in 1927.
[M]echanisms by which it stimulates immune responses remains incompletely understood. Although generally well tolerated, alum may occasionally cause disabling health problems in presumably susceptible individuals.
Animal experiments indicate that biopersistent nanomaterials… e.g. [aluminum particles], can first translocate to draining lymph nodes, and thereafter circulate in blood… and reach the spleen, and, eventually, slowly accumulate in brain.
In 1998, a consortium of French myopathologists described an emerging condition of unknown cause characterized by a pathognomonic lesion at muscle biopsy we called macrophagic myofasciitis (MMF). MMF was detected in middle-aged adult patients with diffuse myalgias and fatigue. Macrophages [were] the major cell type in the lesion… and conspicuously contained aluminium as shown by ionic or X-ray microanalysis.
The crystalline rather than amorphous ultrastructural appearance of the inclusions was suggestive of aluminium hydroxide. Patients had normal renal function and had no peculiar exposure to aluminium other than previous immunization against hepatitis B (HBV), hepatitis A (HAV) or tetanus toxoid (TT) vaccines (100%), thus strongly suggesting that MMF inclusions correspond to aluminium oxyhydroxide (alum), an adjuvant incorporated in these vaccines to boost immunologic responses.
Similar MMF lesions can be detected in the quadriceps muscle in babies and children because this muscle is used for i.m. [intramuscular] vaccine administration in young individuals. MMF can be experimentally reproduced by i.m. vaccination in mice, rats and monkeys…
This point is particularly important in small children who receive numerous alum-containing vaccine shots in the first year of life, increasing risk of chance associations between MMF lesions and unrelated conditions, e.g. congenital myopathies and muscular dystrophies.
[A]bout 1000 patients with documented MMF have been identified in France.
[C]ases have been reported in many other countries.
We recently reviewed the files of 457 adult MMF patients collected from 1994 to 2011…
Patients… had received 1 to 17 i.m. alum-containing vaccine administrations (mean [average] 5.3) in the 10 years before MMF detection…
[O]nset of these clinical symptoms was always posterior to, and delayed from, immunization, median time elapsed from last vaccine administration being 7 months… for initial systemic symptoms, and 11 months… for first myalgia.
In addition to CFS, 15–20% of patients with MMF concurrently develop an autoimmune disease, the most frequent of which being multiple sclerosis (MS)-like demyelinating disorders, Hashimoto’s thyroiditis, and diffuse dysimmune neuromuscular diseases, such as dermatomyositis, necrotizing autoimmune myopathy, myasthenia gravis, and inclusion body myositis.
[I]ndividual susceptibility factors play a crucial role in intolerance to alum.
Adverse response to alum injection may also depend on susceptibility genes… that may favour the development of autoimmune diseases. Thus, aluminium likely represents one environmental factor able to trigger adverse effects in individuals with as yet largely unknown susceptibility genes.
[S]everal closely related conditions have been shown to be associated with [aluminum] overload, including MMF, idiopathic CFS, and MS.
[L]ogically, questions are currently burgeoning about the exact safety level of aluminium adjuvants.
Alum is potentially highly neurotoxic, but it is used at concentrations viewed as an acceptable compromise between adjuvanticity and toxicity by industry and regulatory agencies. In fact, the potential toxicity of alum will be influenced by whether the bioactive nanomaterial remains localized at injection points or rather scatters and accumulates in distant organs and tissues.
A reference study… showed poor Al clearance in the urine after i.m. injection of [aluminum] to rabbits (6% [excreted via urine at 28 days]), and detected Al, in an unknown form, in lymph nodes, spleen, liver, and brain.
Aluminium oxyhydroxide is composed of micron/submicron-sized aggregates of nano-sized (ca 13 nm) particles and these aggregates were initially believed to remain extracellular… We now know that quite the reverse is the case and that APCs avidly take up alum particles…
[W]e examined if fluorescent nanomaterials injected into muscle could translocate to distant organs…
Preliminary results have substantiated this view.
[F]luorescent surrogates of alum particles injected into mouse muscle were rapidly taken up by macrophages… [and a] proportion of particles escaped the injected muscle, mainly within immune cells, gaining access to the regional lymph nodes. Then particle-loaded cells exited the lymphatic system to reach the blood stream… allowing them to gain access to distant organs such as spleen, liver and, eventually, the brain.
Thus, immune cells loaded with alum-like particles circulate after the i.m. injection and can reach distant tissues such as brain…
[I]ncreased attention should be paid to possible long-term neurologic effects of continuously escalating doses of alum-containing vaccines administered to the general population.