Influence of elemental impurities in aluminum hydroxide adjuvant on the stability of inactivated Japanese Encephalitis vaccine, IXIARO®

Schlegl, Robert; Weber, Michael; Wruss, Jürgen; Low, Donald E.; Queen, Kirsten; Stilwell, Shaun; Lindblad, Erik B.; Möhlen, M.

doi:10.1016/j.vaccine.2015.05.103

Cited by 12 publications

(11 citation statements)

References 20 publications

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“…It can be noted, however, that low La presence has been semi-quantitatively found in some 2 w/v% aluminium hydroxide suspensions (Chemtrade Rehydragel ® LV and SPI Pharma Aluminum hydroxide wetgel VAC 20; 0.14 and 0.72 mg/L La, respectively) that are used as adjuvants in vaccines by applying very sensitive ICP-MS techniques. At the same time, the concentrations of Ce, Nd and Sc were below detection limits, <0.0005, <0.002 and <0.01 mg/L, respectively [79].…”

Section: Metals That Do Not Accumulate To Liquormentioning

confidence: 84%

Distribution of Selected Trace Elements in the Bayer Process

Vind

Alexandri

Vassiliadou³

et al. 2018

Metals

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Abstract:The aim of this work was to achieve an understanding of the distribution of selected bauxite trace elements (gallium (Ga), vanadium (V), arsenic (As), chromium (Cr), rare earth elements (REEs), scandium (Sc)) in the Bayer process. The assessment was designed as a case study in an alumina plant in operation to provide an overview of the trace elements behaviour in an actual industrial setup. A combination of analytical techniques was used, mainly inductively coupled plasma mass spectrometry and optical emission spectroscopy as well as instrumental neutron activation analysis. It was found that Ga, V and As as well as, to a minor extent, Cr are principally accumulated in Bayer process liquors. In addition, Ga is also fractionated to alumina at the end of the Bayer processing cycle. The rest of these elements pass to bauxite residue. REEs and Sc have the tendency to remain practically unaffected in the solid phases of the Bayer process and, therefore, at least 98% of their mass is transferred to bauxite residue. The interest in such a study originates from the fact that many of these trace constituents of bauxite ore could potentially become valuable by-products of the Bayer process; therefore, the understanding of their behaviour needs to be expanded. In fact, Ga and V are already by-products of the Bayer process, but their distribution patterns have not been provided in the existing open literature.

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Section: Metals That Do Not Accumulate To Liquormentioning

confidence: 84%

Distribution of Selected Trace Elements in the Bayer Process

Vind

Alexandri

Vassiliadou³

et al. 2018

Metals

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“…Two other organizations, Bharat Biotech (India) and the Institute of Medical Biology/Chinese Academy of Medical Sciences, are running clinical trials of inactivated vaccines, but these are ongoing with no published data as yet. Valneva, based in Scotland, have just expanded their BSL3 manufacturing capacity and have signed a deal with the UK government for 100 million doses of a formaldehyde‐inactivated vaccine adjuvanted with CpG, based on their Japanese encephalitis virus vaccine [151].…”

Section: Inactivated Vaccinesmentioning

confidence: 99%

Vaccines for COVID-19

Tregoning

Brown

Cheeseman

et al. 2020

Clinical and Experimental Immunology

219

204

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The spread of the virus SARS‐CoV‐2, the cause of COVID‐19 has triggered a tidal wave of vaccine development. In the first 9 months since the virus emerged over 200 vaccines have begun pre‐clinical development, 36 of which have entered clinical trials. This review will cover the platforms under assessment, the immune responses underpinning the vaccines, the results so far and the considerations for the next steps.

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“…The wisdom of the use of aluminum in vaccines is now in doubt due to many lines of evidence, including the findings that monocytes pick up aluminum and are signaled to the brain via TNF- and that amyloid is part of amyloid [38][39][40][41]. Metals and proteins form complexes, such as copper/aluminum protein aggregates that are difficult to deal with at a cellular level [42]. Exposures to environmental sources of metallic toxins also reduce the efficacy of vaccines [43].…”

Section: Injury To Endoplasmic Detoxificationmentioning

confidence: 99%

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Lw¹

2018

Autism Open Access

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Neurodevelopmental disorders, including autism spectrum disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene x environment interactions and phenomimicry. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now the rates are so high in some countries that public school programs cannot handle to large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I present a mechanistic biomedical process model (theory) of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism genes" and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, runaway cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload ("ER hyperstress"), contributing to neuronal and glial apoptosis via the unfolded protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal re-toxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to redistribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types o...

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Influence of elemental impurities in aluminum hydroxide adjuvant on the stability of inactivated Japanese Encephalitis vaccine, IXIARO®

Cited by 12 publications

References 20 publications

Distribution of Selected Trace Elements in the Bayer Process

Distribution of Selected Trace Elements in the Bayer Process

Vaccines for COVID-19

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

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