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Biopersistence and brain translocation of aluminum adjuvants of vaccines

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  • Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Biopersistence and brain translocation of aluminum adjuvants of vaccines
    Romain Kroum Gherardi *, Housam Eidi , Guillemette Cr?peaux, Fran?ois Jerome Authier and
    Josette Cadusseau
    Facult? de M?decine and Facult? des Sciences et Technologie, INSERM U955 Team 10, Universit? Paris Est-Cr?teil, Cr?teil, France

    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.We previously showed that poorly 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. The understanding
    of basic mechanisms of particle biopersistence and brain translocation represents a major
    health challenge, since it could help to define susceptibility factors to develop chronic
    neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing
    effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes.
    Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate,
    with variable interindividual efficiency, a dedicated form of autophagy (xenophagy)
    until they dispose of alien materials. Successful compartmentalization of particles within
    double membrane autophagosomes and subsequent fusion with repaired and re-acidified
    lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum
    particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously
    described for infectious particles (HIV, HCV), that obeys to CCL2, signaling the major
    inflammatory monocyte chemoattractant.
    Keywords: alum, vaccine adjuvants, macrophagic myofasciitis, neurotoxicity, genetics, monocytes, CCL2, MCP1

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