Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections

Abstract : Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humansand animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged withfluorescentnanodiamonds were used to evaluate i) the persistence time at the injection site, ii) the translocation of alumfrom the injection site to lymphoid organs, and iii) the behavior of adult CD1 mice following intramuscular injec-tion of alum (400μg Al/kg). Results showed for thefirst time a strikingly delayed systemic translocation of adju-vantparticles. Alum-induced granulomaremained for a very long time in the injected muscle despite progressiveshrinkage from day 45 to day 270. Concomitantly, a markedly delayed translocation of alum to the draininglymph nodes, major at day 270 endpoint, was observed. Translocation to the spleen was similarly delayed(highest number of particles at day 270). In contrast to C57BL/6J mice, no brain translocation of alum was ob-served by day 270 in CD1 mice. Consistently neither increase of Al cerebral content, nor behavioral changeswere observed. On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additionalexperiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at200μg Al/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffu-sion of the adjuvant in lymph nodes and spleen of CD1 mice,and suggests the importance of mouse strain, route ofadministration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants.
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Submitted on : Friday, September 20, 2019 - 10:20:30 AM
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Guillemette Crepeaux, Housam Eidi, Marie-Odile David, Eleni Tzavara, Bruno Giros, et al.. Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections. Journal of Inorganic Biochemistry, Elsevier, 2015, 152, pp.199-205. ⟨10.1016/j.jinorgbio.2015.07.004⟩. ⟨hal-02292714⟩

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