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)
Gardasil: what safety margin did regulators accept?
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
Safety margin at NOAEL
Mouse repeat-dose: ~1450-fold the projected human dose on a body weight basis
“On a body weight basis, the dose of the vaccine administered to mice was approximately 1450-fold the projected human dose.”
NOAEL / key findings
No systemic toxicity; iliac lymph node enlargement/hyperplasia and injection-site inflammation in mice
“There was a treatment-related enlargement of the iliac lymph nodes. Treatment-related microscopic changes were noted in lymph nodes (hyperplasia) and in the muscle at the injection sites (inflammation).”
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 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
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Rat DART study: dose exceeds the human dose 40-fold on a weight-adjusted basis
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