Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Rabbit developmental toxicity study: full antigen dose ≈20x the human dose by body weight (3 kg rabbit, 60 kg human)
Nuvaxovid: what safety margin did regulators accept?
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Safety margin at NOAEL
Rat DART study: dose exceeds the human dose 40-fold on a weight-adjusted basis
“The administered dose was the maximum volume of clinical formulation (used for the early clinical studies) and, although the dose is smaller than the absolute dose that will be administered to humans, it does exceed the human dosage on a weight-adjusted basis by 40-fold.”
NOAEL / key findings
No NOAEL stated; transient CRP and fibrinogen elevations and injection-site inflammation in rabbits, as expected for a vaccine
“Transient elevations of C-reactive protein (CRP) and fibrinogen and local inflammation reactions were observed at the injection sites, indicative of acute reactions as expected.”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)No adverse systemic effects at dosages up to more than 50-fold the human dose (body weight basis)
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)Safety pharmacology only: no cardiorespiratory effects up to 63-fold the human dose (bodyweight basis); no repeat-dose margin stated
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsMouse repeat-dose: ~1450-fold the projected human dose on a body weight basis
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsRat reproduction studies: up to 240 and 160 times the human dose (mg/kg) without fertility or fetal effects
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Monkey NOAEL 0.5 mg/kg CpG adjuvant, >10-fold the clinical mg/kg dose, for systemic immunostimulation
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Rabbit study used RTS,S/AS01B with twice the antigen and adjuvant content of Mosquirix; no numeric margin stated
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsDART: rats given a dose equivalent to the adult human dose; no numeric multiple stated
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Full human dose given to rabbits, with more doses than clinically; no numeric multiple stated
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Not stated in public reviews
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot stated in public reviews
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews