Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Rabbit (repeat-dose toxicity, DART) and rat (DART); mice for immunogenicity only
Cervarix: which tox species, and why?
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
Species
Rabbit (four repeat-dose studies) and rat (one repeat-dose, DART, safety pharmacology); dog for MPL alone
“Four repeated-dose toxicity studies were carried out in rabbits and one in rats.”
Why that species
Rat for DART: predictor of reproductive toxicity and regulatory rodent requirement
“Animal model: As stated by the sponsor, the rat was chosen “because of its use as a predictor of reproductive toxic change in man and the requirement for a rodent species by regulatory agencies.”
Surrogate molecule
No surrogate; toxicity materials comparable in purity to clinical and commercial lots
“Materials used in the non-clinical safety pharmacology, pharmacokinetics and toxicological studies overall had comparable purity levels as the materials used for clinical studies and the materials proposed for marketing.”
Species: general tox
Rabbit (four studies) and rat (one study)
“Four repeated-dose toxicity studies were carried out in rabbits and one in rats.”
Species: DART
Rat (fertility, embryo-fetal, peri/postnatal; vaccine and AS04 alone)
“The reproductive and developmental toxicity of Cervarix and the AS04 adjuvant alone was assessed in a study in female rats of the CD strain. The influence of Cervarix on fertility, embryo-fetal, peri-natal and post-natal survival and development was examined.”
Species: carcinogenicity
Not conducted
“The mutagenic and carcinogenic potential of the Cervarix vaccine was not further evaluated, which is accepted since the vaccine is based on L1 protein and HPV oncoproteins are absent.”
Surrogate used in
No surrogate used; vaccine, AS04 and MPL tested directly
“Pharmacological and toxicological studies were performed on HPV-16/18 L1 VLP AS04, AS04 as well as on MPL.”
Same question, other vaccines
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Rat only
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)Rabbit (repeat-dose toxicity of the vaccine)
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HARat only for repeat-dose toxicity and DART (trivalent RIV3); dog and rat for safety pharmacology
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsMouse (repeat-dose), mouse and rat (single-dose), rat (DART), rabbit (local tolerance)
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsRat only (repeat-dose, fertility/embryo-foetal and postnatal studies)
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsRat (repeat-dose); mouse and rat (single-dose), using the HBsAg-containing combination vaccine HEXAVAC
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Mouse, rat and cynomolgus monkey (repeat-dose); rabbit and baboon escalation studies
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Rabbit (vaccine repeat-dose); rat and rabbit for adjuvant components
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Rabbit for the adjuvanted vaccine; rats and rabbits for Matrix-M1 adjuvant studies
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsRat only
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Rat and rabbit