At any given time, we have 3-4 projects underway.
Project #1. Waning Immunogenicity. Evolution is at work both on vaccine strains and in the wild type. How long before we see waning immunogenicity? We are working on that problem right now. Can we predict when each vaccine will begin to wane in efficacy? (2018/2019)
Project #2. Type Replacement. Systematic review of type replacement in HPV and other vaccines. What is the quality of the study design of studies that do, and do not find type replacement? (2018/2019)
Project #3. Demyelination Diagnosis. Review of diagnosis of autoimmune demyelinating disorders. Review of cause-based diagnosis criteria. (2018/2019)
Project #4. Vaccine risk and vaccine injury diagnosis biomarkers. What are the most promising clinical indicators of risk of vaccine injury, and which indicators might be useful for post-vaccination diagnosis? What clinical interventions might prove effective after vaccine injury? (2018/2019)
You can support these projects best with a monthly donation.
Recent Studies (2017/2018)
(1) Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum (published)
• Aluminum levels in vaccine is based on immune efficacy and ignore body weight for safety.
• Several critical mistakes have been made in the consideration of pediatric dosing of aluminum in vaccines.
• Safety inferences of vaccine doses of aluminum have relied solely on dietary exposure studies of adult mice and rats.
• On Day 1 of life, infants receive 17 times more aluminum than would be allowed if doses were adjusted per body weight.
• Revised MRL calculation based weights are provided, but are also based on derived speculation, not on safety data.
Abstract. FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight. When aluminum doses are estimated from Federal Regulatory Code given body weight, exposure from the current vaccine schedule are found to exceed our estimate of a weight-corrected Pediatric Dose Limit. Our calculations show that the levels of aluminum suggested by the currently used limits place infants at risk of acute, repeated, and possibly chronic exposures of toxic levels of aluminum in modern vaccine schedules. Individual adult exposures are on par with Provisional Tolerable Weekly Intake “limits”, but some individuals may be aluminum intolerant due to genetics or previous exposures. Vaccination in neonates and low birth-weight infants must be re-assessed; other implications for the use of aluminum-containing vaccines, and additional limitations in our understanding of neurotoxicity and safety levels of aluminum in biologics are discussed.
Abstract. 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 the large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I review evidence 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 gene," and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the sampling of environmental toxins, and thus 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, run-away 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 hyper stress), contributing to neuronal and glial apoptosis via the unfolded-protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal retoxification 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 re-distribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types of toxins with secondary, sometime life-threatening comorbidities such as seizures, with overlapping (not mutually exclusive) causality. Reduction of exposure to toxins known to cause mitopathy (mercury) and endoplasmic reticulum dysfunction (mercury and aluminum) during pregnancy and during the early years of development will reduce the risk of ER overload and ER hyper stress, and of ASD diagnosis. This knowledge has immediate clinical translational relevance: post-vaccination symptoms should be heeded as a sign of susceptibility to toxin; Vitamin D can be increased to drive the healthy early phases of the UPR, and mutations in ASD genes encoding proteins with high intrinsic disorder may contraindicate the use of aluminum and mercury for carriers of risk alleles. Clinicians should be alert to a patient’s Vitamin D receptor (BSM) mutational status prior to recommending increased doses. Approaches to improving overall brain health in autistics must be de-stigmatized and given high priority. Reduction of lifetime exposures of industrial and agricultural toxins will improve brain health for the entire human population. Purely genetic studies of ASD, and studies that do not include vaccination as an environmental exposure with potential liability and interactions with genes, are unethical. To qualify as science, studies must test plausible hypotheses, and the absence of association from poorly designed, unethically executed, and underpowered and unsound whole-population association studies have been harmful distractions in the quest for understanding. Skilled paediatricians and ob/gyns will seek evidence of genetic predisposition to environmental susceptibility in the form of non-synonymous substitutions in brain proteins that require ER-folding, and they will provide informed cautions on exposures (from all sources) to environmental toxins to patients and parents of patients with signs of metal and chemical sensitivity. To aid in this, a list of ASD environmental susceptibility protein-encoded genes is presented. A clinical Exome sequence test, followed by loss of function prediction analysis, would point to individuals most susceptible to vaccine metal-induced ER hyper stress leading to failed cellular detoxification.
(3) Endoplasmic Reticulum Hyperstress from Aluminum and Mercury Exposures Drives Autoimmune Diseases of Unknown Origin with a Genetic Risk and Food Allergies (in review)
Abstract. Aluminum and mercury both cause Endoplasmic Reticulum Stress (ER Stress). When combined with genetic variations that lead to protein folding issues in the ER, these metals contribute to ER Hyperstress, including ER Overload and apoptosis. The basic mechanistic exposure of otherwise cryptic potential self-antigens via ER Hyperstress induced cell death leads to immunologic exposure to unusual post-translationally modified proteins. Interrupted protein production means partial (incomplete) acetylation, lipidation, citrullination, and glycosylation. This mode of production of near-self antigen sources is now recognized as crucial for specific autoantibody recognition in autoimmune diseases. Prototypical autoimmune disorders (ADs) like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have a genetic risk, exhibit female predominance, presence of autoantibodies and response to T-cell or B-cell-targeted therapies. Mechanistic evidence exists that shows that they also, without fail, involve pathophysiological outcomes of the Unfolded Protein Response (UPR). Animal models routinely employ injections of aluminum hydroxide as the environmental causal factor to reproduce the symptoms of a surprising number of ADs seen in humans. Human studies have linked aluminum exposures to the onset of ADs, and ER Stress and the Unfolded Protein Response (UPR) both are observed across many ADs in humans. The assumption that low doses of aluminum are not toxic now appears to be incorrect. The literature of autoimmune disorder pathophysiology strongly supports the ER Hyperstress model of autoimmunity, in which generic, otherwise harmless mutations that evoke the UPR, usually to a non-pathophysiological conclusion, contribute to ER Stress that is severely compounded by exposures to metals, including aluminum and mercury. Food allergies also involve ER Hyperstress and are inducible in animals with aluminum hydroxide injections. In a comparison of the protein intrinsic disorder (PID) of proteins known to carry mutations that confer genetic risk of autoimmune disorders to general proteins in the human proteome, the PID of autoimmune-related proteins was significantly lower than that of general proteins (average PID AID vs. PID null 8.58 vs. 16.165, p=0.0003). This result suggests that proteins involved in ADs cannot tolerate non-synonymous substitutions that change folding energies – and it suggests that genetic risk of autoimmunity aided by immune activation will have a cryptic component in which proteins unrelated to the functional aspects of proteins elicit an autoimmune attack. It is predicted that, due to ER Hyperstress and the direct cellular toxicity of metals, autoimmune disorders will also have a component of acquired cellular detoxification deficiency disorder (ACDD), consistent with the oft-reported comorbidity between autoimmune/autoinflammatory disorders and multiple chemical sensitivity. ACDD is a disorder that makes causality assessment challenging but that can be alleviated by aluminum chelation, pointing to ER stress as a shared root cause leading to toxin accumulation. Direct genetic risk exists due to variation in genes involved in detoxification (e.g., HLA and CYP genes), but more generic risk likely exists due to conformational differences in proteins that challenge the unfolded protein response. These realizations point to the importance of mutations in proteins associated with autoimmune disorders cognizant of (upweighting) low protein intrinsic disorder as potential biomarkers of the likely occurrence of autoimmunity following environmental exposures that can trigger ER stress and the UPR. If done well, such mutations may be useful in predicting the specific type of autoimmunity that could occur if exposed to aluminum and mercury containing vaccines and other compounds known to elicit ER stress, such as glyphosate. Overwhelming, convincing evidence supports a genetic susceptibility to aluminum and mercury exposures exist in humans. It must be accepted that some percentage of the population cannot tolerate aluminum exposures as well as others and exposure to aluminum and mercury will caused them to fall into a cascade of events caused by ER Hyperstress. Medicine must shift away from a culture that turns a blind eye to the evidence in support of the fact that AD, NDs and food allergies are caused, in part, by aluminum exposures. Phased biomarker development studies will help Identify the genetic minorities at increased risk of autoimmunity from aluminum and mercury exposure that lead to ER Hyperstress. All future studies of the association of vaccines with autoimmune disorders should focus on the prevalence of autoimmune disorders in vaccinated individuals with known high-risk genotypes compared to individuals without high-risk genotypes, no evidence of familial risk of autoimmunity, and no mutations in the AD-related genes. The entirety of the evidence in the literature supports the clinical existence of ASIA, and ER Hyperstress is a plausible biological mechanism by which genetic variation and injected forms of metals interact to cause autoimmune/ autoinflammatory condition in some people.
(4)Systematic Review of Historical Epidemiologic Studies Influencing Public Health Policies on Vaccination (in review)
Abstract. Numerous agency authorities, resources, and publications cite numerous epidemiological studies as demonstrating a lack of evidence of association between vaccines and autism. Prior analyses have revealed that key studies used by the Institutes of Medicine lack sufficient statistical power to provide confidence that their negative results, i.e., lack of association, could reasonably be due to the combined effects of an inability to detect an association due to low power (attributed to small sample sizes) and to healthy user bias (a form of self-selection in which patients who have previously experienced negative reactions to vaccines opted out of the single vaccine for which association was sought. In this systematic review, 48 “Key Studies” cited by organizations such at the American Association of Pediatrics, or listed by CDC and two reviews as evidence of no association between “Vaccines” and autism, or allegedly demonstrating the ”safety” of thimerosal-containing vaccines (TCV), are independently and collectively reviewed. An objective 11-subscore evaluation score (Objective Evaluation Score; OES) was design that can be applied to any vaccine safety study; the ideal score for any study is +12; the average score for the Key Studies was -6.61. Only two of the forty-eight Key Studies had a non-negative OES. The studies evaluated fell far short of high-quality science: twenty did not estimate ASD prevalence; twenty-two did not study “Vaccinated vs. Unvaccinated”; thirty-two only examine association of a single vaccine; twenty publications studied thimerosal containing vs. non-thimerosal containing vaccines; at least twenty-one studies had insufficient statistical power; thirty-three had evidence of flawed study design; twenty-eight had flaws in the design of analysis, in some cases leading to false negatives on the question of association; thirty-four made unwarranted conclusions about negative results given the sample size and type of study. All but one study were retrospective studies; none were blinded, prospective randomized clinical trials. All fall into the category of correlational analyses. Due to cohort effects and myriad ingrained flaws, correlation studies fail to provide credible evidence capable of definitively falsifying the hypothesis of causality of vaccines and autism and are at the risk of temporal confounding and cohort effects. Studies of single vaccines obviously fail to provide a sufficient level of evidence permitting a generalization to all vaccines or the CDC pediatric vaccination schedule. Studies that did not measure rates or risks of autism were found to be irrelevant to the question. Studies of TCV vs non-TCV found increased health risks due to non-TCVs, but uniformly attributed the result to a mysterious, previously unknown (ad-hoc) health benefit of thimerosal. Low-powered studies cannot be used to support definitive negative evidence, and single-vaccine studies likely suffer from Healthy User Bias. The three largest studies fall into the categories of single-vaccine studies or TCV-vaccines. Many studies adjusted for covariates that should have been considered risk factors; none examined interaction terms between vaccines and plausible co-factors. Combined, these studies have been cited by over 6500 other studies or reviews and form the basis of public health policy and practices. The single meta-analysis conducted included low-powered studies that had already been rejected by the IOM as flawed. None of the studies were designed to test the hypothesis that a heterogeneous subgroup of humans carries susceptibility to neurodevelopmental disorders compared to the general population, nor did any of the studies conducted determine whether such individuals could be detected prior to vaccination. The bolus of studies cited by CDC and AAP conspicuously exclude studies that show a positive association of neurodevelopmental disorders and vaccines. Co-signing organizations and recipients of the of the AAP statement letter to POTUS will be interested to know that the average odds ratio of studies cited was 0.80 (average for ASD-focused studies 0.756); the average odds ratio of studies not cited by these sources was 4.01.
Author’s Conclusion: No studies exist that definitively falsify the vaccine/autism link, and the evidence presented as demonstrating no link and the alleged safety of thimerosal is both extremely weak, and has not been provided to policy makers in an unbiased manner.
(5) Assessment and Analysis of Morbidity and Mortality Rate Estimates from Vaccine Safety Databases, Corrected for Underreporting Bias (completed, being submitted)
Abstract. An analysis of trends in mortality and morbidity in two vaccine safety databases, VAERS and VigiBase, reveals a major jump in reported mortality in the VAERS data for vaccines on the CDC pediatric schedule between 2006-2007, and signals for two major events dominate the implied history of morbidity and mortality in VigiBase in 2001 and 2010. Events antecedent to these dominant signals are discussed. The present analysis suggests that post-market surveillance of vaccine safety using databases of passively collected data is not powerful enough to identify hypotheses of serious problems with vaccines. Serious flaws exist in the data capture, data representation, and point-of-care utilization (reporting). The CDC’s more comprehensive Vaccine Safety Database (VSD) is not readily available for independent analyses, which severely limits the number, type, design, and reproducibility of VSD studies. Because causality can never be assessed from passive reporting systems, is is therefore concluded that long-term post-market surveillance vaccine safety science does not exist. VSD data should be released for unrestricted analyses, and our society requires mandated, active, automated reporting with penalties to practitioners who fail to report.
All of this research was funded by donations from the public to IPAK. You can help drive our studies forward best with a monthly donation.