Journal of Trace Elements in Medicine and Biology 62 (2020) 126632

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Journal of Trace Elements in Medicine and Biology

journal homepage: www.elsevier.com/locate/jtemb

The role of aluminum adjuvants in vaccines raises issues that deserve T

independent, rigorous and honest science⋆
Guillemette Crépeauxa,b,*, François-Jérôme Authiera, Christopher Exleyc, Lluís Lujánd,e,
Romain K. Gherardia
a
Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
b
EnvA, IMRB, F-94700 Maisons-Alfort, France
c
The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, ST5 5BG, United Kingdom
d
Department of Animal Pathology, University of Zaragoza, Spain
e
Instituto Universitario de Investigación Mixto Agroalimentario de Aragón (IA2), University of Zaragoza, Spain

In their recent review on aluminum and vaccines [1], JP Goullé & L phagocytosed after injection, and selectively concentrate with very long
Grangeot-Keros described general knowledge on aluminum (Al) ex- residence time in immune cells which represent a very small but highly
posure, kinetics and toxicity but made very little effort to delineate the reactogenic cell compartment (for review see [6]). Isotopic 26Al hy-
scientific questions specifically related to Al adjuvants in vaccines. In- droxide adjuvant studies indicate that a single vaccine dose adminis-
stead of representing the bulk of their review, the subject of Al ad- tered through im injections to an adult rabbit will induce a small in-
juvants covered no more than one third of the 3 page-text. Numerous crease of 0.8 % in plasma concentration, masked by the Al background,
important papers on the topic were omitted, i.e. 20 years of scientific with cumulative Al excretion becoming quasi-flat a few days after in-
publications in clinical, post-mortem, in vitro and in vivo experimental jection [7]. This is due to the insolubility of Al hydroxide and explains
studies published by independent research teams, worldwide experts in why increased Al is not found in blood and hair of vaccine recipients
this topic, were simply omitted. [8]. This represents a legitimate reason of concern since instead of
For instance, in 2018, a critical analysis of reference studies on Al being efficiently eliminated the insoluble crystalline particulate ad-
adjuvant toxicokinetics revealed their extreme paucity, several major juvant persists intra-cellularly. In contrast to the opposite contention
methodological weaknesses, and profound misconception of the fate of made by Goullé and Grangeot-Keros, it has been repeatedly shown, in
injected Al adjuvants [2]. The Goullé and Grangeot-Keros review suffers both mouse and sheep, that Al particles exit the injection site to reach
from the same fundamental misunderstanding of the question. Specia- the draining lymph nodes and spleen and more distant organs like the
lized Al toxicologists have now recognized that comparing toxicological central nervous system [9–14]. There is no reason to believe that the
properties of different forms of Al (soluble vs particulate) administered adjuvant particles translocated beyond the vaccine injection site lose
by different routes (oral vs intramuscular (im) or intravenous) is in- their immunogenic properties and are non-toxic.
correct [3]. In the case of Al adjuvants such comparisons are misleading Goullé and Grangeot-Keros focused on the lack of detectable in-
and therefore inadmissible [2]. Goullé and Grangeot-Keros stated that, crease of Al plasma levels following Al adjuvant injections and so ap-
similarly to lead for instance, “only biologically measurable excessive parently ignored that increased Al tissue levels have been indeed re-
levels of aluminium in the organism can be potentially toxic”. Such a peatedly reported following Al adjuvant or adjuvanted vaccines
sweeping statement of classical toxicology may be in line with the “dose injections, in rabbit brains [7], in mouse brains [11], in rat bones and
makes the poison” paradigm but does not correspond to the true si- brains [15], and in sheep draining lymph nodes and spinal cord
tuation when, for example, i) particulate forms of metals are con- [13,14]. This was observed despite a marked dilution effect linked to
sidered; ii) specific intracellular capture is involved. Moreover Al in the selective distribution of Al particles to a limited microglial cell
vaccines do not represent low doses, especially for babies [4,5]. Let us compartment.
ironically state that a man shot dead by a lead bullet does not die from Other “reassuring” claims of Goullé and Grangeot-Keros were re-
saturnism (lead toxicity!). In contrast to soluble dietary Al reaching the lated to clinical studies. They dismissed the fact that Al-containing
blood across the intestinal barrier and excreted in urine, Al hydroxide vaccines may be associated with myalgia, chronic fatigue syndrome and
adjuvant particles are nearly insoluble at pH 7.35 [2]. They are rapidly cognitive impairment typically observed in patients with Al hydroxide

⋆
Comments on the review « Aluminum and vaccines: Current state of knowledge, Aluminium et vaccins, ce que l’on sait aujourd’hui » by J.-P. Goullé & L.
Grangeot-Keros, Médecine et maladies infectieuses, 2019.
⁎
Corresponding author at: Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France.
E-mail address: [email protected] (G. Crépeaux).

https://doi.org/10.1016/j.jtemb.2020.126632
Received 3 July 2020; Received in revised form 22 July 2020; Accepted 29 July 2020
0946-672X/ © 2020 Elsevier GmbH. All rights reserved.