Biomedical ethics requires that clinical trial participants be accurately informed of the potential risks associated with investigational medical products. We found that the vaccine manufacturer Merck made false statements to the trial participants about the safety of Gardasil in its Future II HPV vaccine trial in Denmark. The clinical study protocol specified that safety testing was one of the trial’s primary objectives, but the recruitment brochure given to trial participants stated this was not the case, as allegedly the vaccine had (...) already been proven safe in previous trials. The advertising material for the trial and the informed consent forms stated that the comparator was saline or an inactive substance, when, in fact, it contained Merck’s proprietary aluminum adjuvant which is highly immunogenic. Several trial participants experienced long-term disabling symptoms during the trial, also some randomized to the adjuvant “placebo” control group. In all cases, their serious adverse events were dismissed as unrelated to the study treatment by Merck’s clinical investigators. We demonstrate that Merck’s published statements about the safety of their proprietary aluminum adjuvant is contradicted by the research evidence. The use of adjuvants as “placebos” in vaccine clinical trials is unethical as it makes it difficult to discover serious vaccine harms. (shrink)

Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll‐like (...) receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T‐ and B‐lymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS‐CoV‐2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID‐19 vaccinations could launch a new era of personalized healthcare. (shrink)

In 2022, students at North American universities with third-dose COVID-19 vaccine mandates risk disenrolment if unvaccinated. To assess the appropriateness of booster mandates in this age group, we combine empirical risk-benefit assessment and ethical analysis. To prevent one COVID-19 hospitalisation over a 6-month period, we estimate that 31 207–42 836 young adults aged 18–29 years must receive a third mRNA vaccine. Booster mandates in young adults are expected to cause a net harm: per COVID-19 hospitalisation prevented, we anticipate at least (...) 18.5 serious adverse events from mRNA vaccines, including 1.5–4.6 booster-associated myopericarditis cases in males (typically requiring hospitalisation). We also anticipate 1430–4626 cases of grade ≥3 reactogenicity interfering with daily activities (although typically not requiring hospitalisation). University booster mandates are unethical because they: (1) are not based on an updated (Omicron era) stratified risk-benefit assessment for this age group; (2) may result in a net harm to healthy young adults; (3) are not proportionate: expected harms are not outweighed by public health benefits given modest and transient effectiveness of vaccines against transmission; (4) violate the reciprocity principle because serious vaccine-related harms are not reliably compensated due to gaps in vaccine injury schemes; and (5) may result in wider social harms. We consider counterarguments including efforts to increase safety on campus but find these are fraught with limitations and little scientific support. Finally, we discuss the policy relevance of our analysis for primary series COVID-19 vaccine mandates. (shrink)