Aluminum Adjuvants in Vaccines - Safety, Route of Exposure, and Biopersistence In the Body - Key Excerpts from Vaccines and Autoimmunity 2015
Here are all the important highlights with references to help you with arguing that aluminum adjuvants in vaccines have not been adequately safety tested in human beings, and to the contrary have been demonstrated in animal models and experiments that they are obscenely toxic and directly causal in numerous pathologies, especially those pertaining to autoimmunity and systemic inflammatory disorders.
Anyone who tells you that aluminum adjuvants have been safely used for 100 years is either lazy and hasn't read the research, or is severely dishonest.
How is the safety of Al regulated?
>While the US Food and Drug Administration (FDA) does set an upper limit for Al in vaccines at no more than 850 μg/dose (Baylor et al., 2002), it is important to note that this amount was selected empirically from data showing that Al in such amounts enhanced the antigenicity of the vaccine, rather than from existing safety data or on the basis of toxicological considerations (Baylor et al., 2002).
>It is also of note that the FDA Department of Health and Human Services (DHHS) requires limits on Al in parenteral feeding solutions and requires warning labels about potential Al hazards, yet sets no safety limits or required warnings for Al in vaccines (US FDA DHHS, 2005).
>The consequence of this view is best reflected in the fact that a large number of vaccine trials use an Al adjuvant-containing placebo or another Al-containing vaccine as the “control group,” despite much evidence showing that Al in vaccine-relevant exposures is toxic to humans and animals (Gherardi et al., 2001; Couette et al., 2009; Li et al., 2009; Shaw and Petrik, 2009; Passeri et al., 2011; Shaw et al., 2013) and that, therefore, its use as a placebo in vaccine trials is scientifically untenable (Exley, 2011).
>That the safety issue of Al in vaccines has indeed been overlooked by the regulators (for more than 90 years while these compounds have been in use) is illustrated by the following statement from the World Health Organization (WHO) Special Committee on the Safety of Vaccines (WHO, 2005): “The Committee considered the safety of adjuvants used in vaccines. This hitherto neglected subject is becoming increasingly important given modern advances in vaccine development and manufacture.”
Dietary versus vaccine-derived Al: is there a difference?
>Although Al is clearly neurotoxic, a common assertion is that humans obtain much more Al from diet than from vaccines, and that, therefore, the adjuvant form of Al does not represent a toxicological risk (Offit and Jew, 2003). However, this notion contradicts basic toxicological principles. For instance, it should be obvious that the route of exposure which bypasses the protective barriers of the gastrointestinal tract (GIT) and/or the skin will likely require a much lower dose to produce a toxic outcome. In the case of Al, only ∼0.25% of dietary Al is absorbed into systemic circulation (Yokel et al., 2008), and it is rapidly filtered by the kidneys in those with healthy kidney function. In contrast, Al hydroxide (the most common adjuvant form) injected intramuscularly may be absorbed at nearly 100% efficiency over time (Yokel and McNamara, 2001) and follows a completely different route in the body (i.e. accumulation in other organs, including the spleen and the brain) (Khan et al., 2013).
>It is further important to note that although the half-life of enterally or parenterally absorbed Al from the body is short (approximately 24 hours), the same cannot be assumed for Al adjuvants in vaccines, as Al is tightly complexed to the vaccine antigen. Although the tightness of bonding between the Al adjuvant and the antigen is considered a desired feature, as it enhances the immunogenicity of vaccines (Egan et al., 2009), this feature represents an additional problem for effective clearance of Al from the body, as the size of most Al-adsorbed antigen complexes is greater than the molecular weight cut-off of the glomerulus (Tomljenovic and Shaw, 2011). Experiments in adult rabbits demonstrate that even in an antigen-free form, Al hydroxide, the most commonly used adjuvant, is poorly excreted. The cumulative amount of Al hydroxide excreted in the urine of adult rabbits as long as 28 days post-intramuscular injection was less than 6%, as measured by accelerator mass spectrometry (Hem, 2002).
>Moreover, current research shows that, other than antigens, Al can form complexes with other vaccine excipients. Recently, Lee (2013a) explored the melting profiles of the residual HPV L1 gene DNA contaminant recently detected in the quadrivalent HPV vaccine Gardasil.
>Finally, the latest research shows that peripherally injected Al adjuvant nanoparticles engulfed by macrophages actively spread throughout the body, eventually crossing the BBB and blood–CSF barrier (Khan et al., 2013). Once in the CNS, Al adjuvant nanoparticles incite deleterious inflammatory responses, resulting in a range of neuropathological effects (Petrik et al., 2007; Shaw and Petrik, 2009). It should be noted that Al on its own can alter the properties of the BBB (Banks and Kastin, 1989; Zheng, 2001; Yokel, 2006), making the brain more accessible to inflammatory and immune mediators. Al also increases endothelial adhesion of activated monocytes (Oesterling et al., 2008), which, in the case of Al penetration in the CNS, can likewise facilitate the entry of immune-competent cells into the CNS and lead to adverse manifestations. In accordance with these observations, Zinka et al. (2006) reported six cases of sudden infant death that occurred within 48 hours after vaccination with hexavalent vaccines. The post-mortem analysis of the six children, aged 4–17 months (five of whom were vaccinated with Hexavac and one with Infanrix Hexa), revealed abnormal pathologic findings, particularly affecting the nervous system. The overall pathological abnormalities included acute congestion, defective BBB, infiltration of the leptomeninx by macrophages and lymphocytes, perivascular lymphocytic infiltration, diffuse infiltration of the pons, mesencephalon, and cortex by T-lymphocytes, microglia in the hippocampus and pons, and, in one case, necrosis in the cerebellum (Zinka et al., 2006).
Long-term persistence of Al adjuvants in the body and its effects
>The prolonged hyperactivation of the immune system and chronic inflammation triggered by repeated exposure and unexpectedly long persistence of Al adjuvants in the human body (up to 11 years post-vaccination: Gherardi et al., 2001; Ryan et al., 2006; Shivane et al., 2012) are thought to be the principal factors underlying the toxicity of these compounds. One of the reasons for this long retention of Al adjuvants in bodily compartments, including systemic circulation, is most likely its tight association with the vaccine antigen or other vaccine excipients (i.e. contaminant DNA), as already explained. Even dietary Al has been shown to accumulate in the CNS over time, producing Alzheimer-type outcomes in experimental animals fed equivalent amounts of Al to what humans consume through a typical Western diet (Walton, 2007; Walton and Wang, 2009).
>The long retention of Al adjuvants was first identified, and has since been extensively studied, in macrophagic myofasciitis (MMF) patients. MMF is a condition characterized by highly specific myopathological alterations at deltoid muscle biopsy, first recognized in 1998, and subsequently shown to result from long-term persistence of vaccine-derived Al hydroxide nanoparticles within macrophages at the site of previous vaccine injections.
>Another point requiring emphasis is that the bioaccumulation of Al in the brain appears to occur at a very low rate in normal conditions, thus potentially explaining the presumably good overall tolerance of this adjuvant despite its strong neurotoxic potential. Nonetheless, according to Khan et al. (2013), continuously increasing doses of the poorly biodegradable Al adjuvant may become “insidiously unsafe,” especially in cases of repetitive closely-spaced vaccinations (otherwise known as “vaccine rechallenge”) and in those with an immature/altered BBB, such as the very young or those suffering past head injuries. In this context, the latest research by Lujan et al. (2013), who described a severe neurodegenerative syndrome in commercial sheep, linked to the repetitive inoculation of Al-containing vaccines, is noteworthy. In particular, the “sheep ASIA syndrome” mimics in many aspects human neurological diseases linked to Al adjuvants (Lujan et al., 2013). The adverse chronic phase of this syndrome affects 50–70% of flocks and up to 100% of animals within a flock. It is characterized by severe neurobehavioural outcomes, all of which are consistent with Al toxicity (restlessness, compulsive wool biting, generalized weakness, muscle tremors, loss of response to stimuli, ataxia, tetraplegia, stupor, coma, and death), inflammatory lesions in the brain, and the presence of Al in CNS tissues (Lujan et al., 2013). The main histopathologic change in the chronic phase of sheep ASIA syndrome is located at the spinal cord and consists of multifocal neuronal necrosis and neuron loss in both dorsal and ventral column of the gray matter.
>These findings by Lujan et al. (2013) are consistent with those of Shaw and Petrik (2009) and Khan et al. (2013), who both demonstrated the ability of Al adjuvants to penetrate the blood–CSF barrier and BBB. More significantly, the quoted research also shows that the resulting presence of Al in the brain can trigger severe neurological damage, with devastating consequences. Collectively, these findings also explain in part why the majority of reported adverse reactions following vaccinations with adjuvanted vaccines are neurological and neuropshychiatric with an underlying immunoinflammatory or autoimmune component (Konstantinou et al., 2001; Carvalho and Shoenfeld, 2008; Couette et al., 2009; Passeri et al., 2011; Zafrir et al., 2012).
In summary
It is clear from the previously quoted research that the toxicity potential of Al will be influenced by its biopersistence and its biodistribution (i.e. whether the bioactive Al adjuvant nanoparticles remain localized at injection sites or scatter and accumulate in distant organs and tissues). All the clinical and experimental evidence collected thus far identifies at least three main risks associated with Al in vaccines:
1. it can persist in the body (up to 11 years following vaccination);
2. it can trigger pathological immunological responses;
3. it can make its way into the CNS, where it can drive further deleterious immunoinflammatory processes, resulting in brain inflammation and long-term neural dysfunction.
Chapter 4 - Pages 43-48
Shoenfeld, Y., Agmon-Levin, N., & Tomljenovic, L. (Eds.). (2015). Vaccines and Autoimmunity. doi:10.1002/9781118663721
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