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)
Mosquirix: what safety margin did regulators accept?
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)
Safety margin at NOAEL
Rabbit study used RTS,S/AS01B with twice the antigen and adjuvant content of Mosquirix; no numeric margin stated
“The tested RTS,S/AS01B formulation consists of 50 μg of RTS,S antigen combined with AS01B containing 50 μg of MPL and 50 μg of QS-21 in liposomes and therefore contains twice the amounts of these constituents than the RTS,S/AS01E (Mosquirix) candidate vaccine.”
NOAEL / key findings
No NOAEL stated; dose-related acute injection-site inflammation, fully recovered 28 days after last dose; no systemic toxicity
“In conclusion, intramuscular administration of RTS,S/AS01B on four occasions at 2-week intervals triggered an acute inflammatory response at injection sites that increased with the vaccine dose and volume administered. Nonetheless, full recovery was observed 28 days after the last administration.”
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
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