Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy?
Authors: Christopher A Shaw
Dan Li
Lucija Tomljenovic
Journal: Immunotherapy (2014)
Discipline: IMMUNOLOGY
Keywords: CNS; adjuvant; aluminum; autoimmunity; neurodegeneration
Affiliations: Neural Dynamics Research Group, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada.

Abstract:  In spite of a common view that aluminum (Al) salts are inert and therefore harmless as vaccine adjuvants or in immunotherapy, the reality is quite different. In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as vaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential impact for triggering autoimmunity. Autoimmune and inflammatory responses affecting the CNS appear to underlie some forms of neurological disease, including developmental disorders. Al has been demonstrated to impact the CNS at every level, including by changing gene expression. These outcomes should raise concerns about the increasing use of Al salts as vaccine adjuvants and for the application as more general immune stimulants. 

Retracted: No

PubPeer comments:
 Figure 1 here: ![file] Reused as Figure 1 in Li et al.,  Subcutaneous injections of aluminum at vaccine adjuvant levels activate innate immune genes in mouse brain that are homologous with biomarkers of autism (2017) -- see [sepaarate thread] . ![file] Here values and error bars were computed for measurements from three male mice in each of the control and Al-exposed groups, but did not change when that became five mice in each group in 2017. As [noted here] , the Figure also appeared in **another** 2014 paper by the same group,  Etiology of autism spectrum disorders: Genes, environment, or both? ![file] , 
 Can any statisticians comment on the validity of confidence bounds calculated for distributions consisting of b three samples b , and the propriety of using a t-test to compare a pair of three-sample distributions? , 
 The data in figure 1D shows that 8 different groups have been compared to the control group and a t test is used instead of a multi-group test like ANOVA. Therefore a bonferroni correction should be applied. With 8 different comparisons, that would require a p value of (approximately) 0.05 8 = 0.006. With that threshold none of the groups are significant. , 
 hey how about they used a different test to compare 3 means? , 
 blockquote 8 different groups have been compared to the control group and a t test is used blockquote But one of those bars in 1D is for the  housekeeping protein ACT, it s there as a standard. More precisely: the authors begin with 17 candidate RNAs proteins plus ACT. They have semi-quantitative gene-expression results in Fig 1B, expressed as a mean of three ratios... three treatment mice have been randomly paired with three control mice, and the relative RNA measurements **within that random pair** converted into a ratio. This strikes me as a bizarre way of processing data, as any other of the six possible pairings would have given three different ratios. Is this normal practice? Anyway, this  distribution of three ratios is converted into a mean and confidence limits. WHY NOT JUST PLOT THE VALUES!? And compared to 0 with a one-sided t-test. Yes, really, I am not making this up. Having caught 7 proteins in this fishing expedition in 1B, the authors repeat the bizarro-world statistics with the semi-quantitative protein measurements in 1D, treating this as an **independent confirmation** (as if the amount of proteins expressed by a given RNA is **independent** of the amount of that RNA). More strangely still, despite the semi-quantitative nature of these measurements, the distributions from each three protein-ratio pairs in 1D is almost identical to the corresponding RNA-ratio in 1B. For instance, the Al Control ratios of TNF-A have a mean of 3 + - 1 in 1B (p lt; 0.05), and a mean of 3 + - 1 in 1D (p lt; 0.01). How likely is this? It is especially strange as the level of protein TNF-A for the 3rd control mouse in Fig 1C is unambiguously 0. There is **no protein there at all**. That band might as well have been blanked with Photoshop. So the Al Control ratio of TNF-A for that pair is infinity. ![] How do you get SEM bars of +-1 when **one value in the distribution is infinity**? I would have posted this earlier, but I had to read the description several times to reassure myself that the statistics were indeed this crazy. , 
 Corrigendum, April 2019 (behind a pay-wall): https: www.ncbi.nlm.nih.gov pubmed 30860442  **Corrigendum** In the Perspective Article by Christopher A Shaw, Dan Li and Lucija Tomljenovic, titled u2018Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy?u2019, which appeared in the November 2014 issue of Immunotherapy 6(10), 1055u20131071 (2014), some of the data in Figure 1 has been brought into question. Therefore, the figure has been removed at the request of the author and with the agreement of the journal editor. The editors and authors of Immunotherapy would like to sincerely apologize for any confusion this may have caused our readers. One of the questions raised about  the data in Figure 1 is their uncredited re-use from [Li et al (2017)] as if they were new results. There are of course **many other questions** about the data, resulting in the retraction of Li et al. for fabrication ( This article has been retracted at the request of the Editor-in-Chief and Authors, due to evidence of incorrect data. The data of gel images in several figures (Fig. 2A and C and Fig. 4 A, B, C and D) are incorrectly presented ). Those other questions are discussed in the [corresponding PubPeer thread] . But apart from the self-plagiarism of fabricated data, the editors of Immunotherapy are comfortable with the paper. ,