Shingrix by GlaxoSmithKline (Zoster)

*"Placebo" is defined as 0.9% saline solution.

However, nearly a third of subjects receiving placebo in one Shingrix clinical trial experienced adverse events within 30 days post-vaccination.

Possible explanations for relatively high percentage of placebo recipients reporting adverse events:

The Nocebo Effect & side effects of normal saline injection.

"[T]he widely varying rates of adverse effects reported by patients taking placebo and the high prevalence of such symptoms in the general population should be considered by both trialists and clinicians. In addition, variability of adverse effect ascertainment is considerable and suggests the need for better standardization in research."

Source: Medication-Attributed Adverse Effects in Placebo Groups

More information on the AS01B adjuvant:

"The adjuvant system used in the candidate vaccine is AS01 (GlaxoSmithKline Vaccines), a liposome-based adjuvant system containing the immunoenhancers 3-O-desacyl-4′-monophosphoryl lipid A (MPL), and the saponin QS-21 (Quillaja saponaria Molina, fraction 21."

Reference, here.

Monophosphoryl Lipid A (MPLA)-Containing Liposomes:
"Liposomes are closed bilayer membranes containing an entrapped aqueous volume... Suitable hydrophilic polymers for surrounding the liposomes include... PEG [used in Pfizer's COVID vaccine]..."

"...a typical monophosphoryl lipid A (MPLA)-containing liposome (L(MPLA)) is the one originally referred to as Walter Reed liposomes but now known as Army Liposome Formulation (ALF), as a vaccine adjuvant."

Reference, here.

Saponin [Quillaja saponin from the Soapbark tree]:
"Since saponins interact with the cholesterol of cell membranes and, consequently, cause membrane damage, cell lysis, and necrosis, they present high toxicity for clinical practice."

QS-21:
"...QS-21 toxicity [has] been studied. For most patients the dose-limiting toxicity is about 50 [micrograms per dose]... Therefore, the safety of Quillaja saponins is still not well established and more studies are necessary."

"The lowest optimal immunogenic dose [of QS-21] was 10 [micrograms]."

"Local pain and post vaccination myalgias were greater in individuals that received QS-21. Despite increased serum antibodies, the mean titers for formulations (with or without QS-21) were not different."

Reference, here.

"The QS-21 imparts unique properties in that it binds to the liposomal cholesterol where it causes perforations (holes) or other permanent structural changes in the liposomes... A reduced amount of free QS-21 presumably resulted in reduced local injection pain often caused by free QS-21."

Reference, here.