Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats

Weisser K, Göen T, Oduro JD, Wangorsch G, Hanschmann KMO, Keller-Stanislawski B (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Archives of Toxicology Springer

Book Volume: 93

Pages Range: 2787-2796

Journal Issue: 10

DOI: 10.1007/s00204-019-02561-z

Abstract

Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC(0-80 d), mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.

Authors with CRIS profile

Thomas Göen Lehrstuhl für Arbeits-, Sozial- und Umweltmedizin

Involved external institutions

Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) DE Germany (DE) preclinics GmbH DE Germany (DE)

How to cite

APA:

Weisser, K., Göen, T., Oduro, J.D., Wangorsch, G., Hanschmann, K.M.O., & Keller-Stanislawski, B. (2019). Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats. Archives of Toxicology, 93(10), 2787-2796. https://doi.org/10.1007/s00204-019-02561-z

MLA:

Weisser, Karin, et al. "Aluminium in plasma and tissues after intramuscular injection of adjuvanted human vaccines in rats." Archives of Toxicology 93.10 (2019): 2787-2796.

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