Aluminium adjuvants used in vaccines versus placebo or no intervention

Djurisic, Snezana; Jakobsen, Janus Christian; Petersen, Susanne; Kenfelt, Mette; Gluud, Christian

doi:10.1002/14651858.cd012805

Cited by 12 publications

(13 citation statements)

References 87 publications

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“…There is considerable current interest in the potential for Al to produce reproductive toxicity, fueled in part by the controversy concerning its safety as an adjuvant in vaccines. This has been addressed by the proposed Cochrane Library assessment of the benefits and harms of Al adjuvants used in vaccines versus placebo or no intervention (Djurisic et al 2017;Weisser et al 2017).…”

Section: Value Of This Reviewmentioning

confidence: 99%

Aluminum reproductive toxicity: a summary and interpretation of scientific reports

Yokel

2020

Critical Reviews in Toxicology

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Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and rats was evident after exposure to !25-fold the amount of Al consumed in the diet. Generally, the additional daily Al systemic exposure of studies that reported statistically significant results was greater than 100-fold above the typical human daily Al dietary consumption equivalent. Male reproductive endpoints were significantly affected after exposure to lower levels of Al than females. Increased Al intake increased fetus, placenta, and testes Al concentrations, to a greater extent in the placenta than fetus, and, in some cases, more in the testes than placenta. An adverse outcome pathway (AOP) was constructed for males based on the results of the reviewed studies. The proposed AOP includes oxidative stress as the molecular initiating event and increased malondialdehyde, DNA and spermatozoal damage, and decreased blood testosterone and sperm count as subsequent key events. Recommendations for the design of future studies of reproductive outcomes following exposure to Al are provided.

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Section: Value Of This Reviewmentioning

confidence: 99%

Aluminum reproductive toxicity: a summary and interpretation of scientific reports

Yokel

2020

Critical Reviews in Toxicology

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“…The rate of serious adverse events was low for both vaccine and control groups in the studies included in the current review. However, the benefits and harms of aluminium‐containing adjuvants are being further assessed in a Cochrane Review (Djurisic 2017), and research is underway to determine how suitable they are as control vaccines for RCTs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males

Bergman

Buckley

Villanueva

et al. 2019

Cochrane Database of Systematic Reviews

101

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“…The unknown consequences of aluminum-containing adjuvants, more generally, is concerning. A Cochrane review is currently underway to determine whether any RCTs exist which evaluated the effects of aluminium adjuvants compared with placebo or no intervention 41…”

Section: Discussionmentioning

confidence: 99%

Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology

Doshi

Bourgeois

Hong

et al. 2020

BMJ EBM

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PurposeTrustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine’s risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials.MethodsWe assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms.ResultsAcross data sources, the control was inconsistently reported as ‘placebo’-containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an ‘inactive’ substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the ‘safety profile of (AAHS) is well characterised’.ConclusionsThe stated rationale of using AAHS control—to characterise the safety of the HPV virus-like particles—lacks clinical relevance. A non-placebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns.Trial registration numbersNCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.

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Aluminium adjuvants used in vaccines versus placebo or no intervention

Cited by 12 publications

References 87 publications

Aluminum reproductive toxicity: a summary and interpretation of scientific reports

Aluminum reproductive toxicity: a summary and interpretation of scientific reports

Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males

Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology

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