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)
Fendrix: what safety margin did regulators accept?
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
Safety margin at NOAEL
Safety pharmacology only: no cardiorespiratory effects up to 63-fold the human dose (bodyweight basis); no repeat-dose margin stated
“A safety pharmacology study did not show any effect on respiratory or cardiovascular parameters when the HBsAg was administered intravenously or when the HB-AS04C vaccine was given intramuscularly, up to a 63-fold of the human dose expressed on a bodyweight basis.”
NOAEL / key findings
No NOAEL stated; minor dose-related immunostimulatory effects with MPL; minor reversible injection-site inflammation in rabbit
“The effects seen were minor and consistent with an immunostimulatory action. The minor effects seen were dose-related.”
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)
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
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