title: Aluminum adjuvants of vaccines injected into the muscle: Normal fate, pathology and associated disease.
abstract: Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out.
authors.affiliation: Garches-Necker-Mondor-Hendaye Reference Centre for Neuromuscular Diseases, 94000 Créteil, France; Expert Centre for Neuromuscular Pathology, Henri-Mondor Hospital, AP-HP, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France; Inserm U955-Team 10 "Biology of Neuromuscular System" Paris Est-Créteil University, Créteil, France.
authors.forename: R K
authors.initials: RK
authors.lastname: Gherardi
authors.affiliation: Garches-Necker-Mondor-Hendaye Reference Centre for Neuromuscular Diseases, 94000 Créteil, France; Expert Centre for Neuromuscular Pathology, Henri-Mondor Hospital, AP-HP, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France; Inserm U955-Team 10 "Biology of Neuromuscular System" Paris Est-Créteil University, Créteil, France.
authors.forename: J
authors.initials: J
authors.lastname: Aouizerate
authors.affiliation: Garches-Necker-Mondor-Hendaye Reference Centre for Neuromuscular Diseases, 94000 Créteil, France; Inserm U955-Team 10 "Biology of Neuromuscular System" Paris Est-Créteil University, Créteil, France.
authors.forename: J
authors.initials: J
authors.lastname: Cadusseau
authors.affiliation: Garches-Necker-Mondor-Hendaye Reference Centre for Neuromuscular Diseases, 94000 Créteil, France; Inserm U955-Team 10 "Biology of Neuromuscular System" Paris Est-Créteil University, Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Yara
authors.affiliation: Garches-Necker-Mondor-Hendaye Reference Centre for Neuromuscular Diseases, 94000 Créteil, France; Expert Centre for Neuromuscular Pathology, Henri-Mondor Hospital, AP-HP, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France; Inserm U955-Team 10 "Biology of Neuromuscular System" Paris Est-Créteil University, Créteil, France. Electronic address: authier@u-pec.fr.
authors.forename: F J
authors.initials: FJ
authors.lastname: Authier
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis; D003072:Cognition Disorders / Q000209:etiology; D003140:Communicable Disease Control / Q000379:methods; D045604:Extracellular Fluid / Q000737:chemistry; D005208:Fasciitis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D005221:Fatigue / Q000209:etiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007273:Injections, Intramuscular; D000069451:Long Term Adverse Effects / Q000139:chemically induced; D008264:Macrophages / Q000648:ultrastructure; D059352:Musculoskeletal Pain / Q000209:etiology; D009220:Myositis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D018923:Persian Gulf Syndrome / Q000139:chemically induced; D018418:Th2 Cells / Q000187:drug effects; D014612:Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D014612:Vaccines; D000536:Aluminum Hydroxide
keywords: Aluminum; CCL2; Chronic fatigue syndrome; Cognitive dysfunction; Dysfonction cognitive; Granuloma; Granulome; Myalgias; Myalgies; Myofaciite; Myofasciitis; PET-scan; SPECT; Syndrome de fatigue chronique; TEP scan; Vaccines; Vaccins