Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Rabbit (repeat-dose toxicity, DART) and rat (DART); mice for immunogenicity only
HBVaxPro: which tox species, and why?
hepatitis B vaccine (rDNA) · HBsAg VLPs
Species
Rat (repeat-dose); mouse and rat (single-dose), using the HBsAg-containing combination vaccine HEXAVAC
“The absence of toxicity was evaluated after repeated administrations in the rat according to treatment schedules mimicking a human vaccination scheme (i.e., 3 injections at monthly intervals).”
Why that species
Not stated in public reviews
The reviews list the species but not why. For biologics, ICH S6(R1) asks for species in which the product is pharmacologically active (target binding and activity), usually a cynomolgus monkey.
“A relevant species is one in which the test material is pharmacologically active due to the expression of the receptor or an epitope (in the case of monoclonal antibodies).”
✓ VerifiedICH 2011: ICH S6(R1): Preclinical Safety Evaluation of Biotechnology-Derived…, p. 7Source ↗
Surrogate molecule
No surrogate; thiomersal-free HBsAg bulk tested as part of the HEXAVAC combination vaccine
“The tested substance was Hep B Thiomersal-Free Bulk Vaccine as Part of HEXAVAC development which was carried out in accordance with the current guideline (CPMP/SWP/465/95) for preclinical pharmacological and toxicological testing of vaccines.”
Species: general tox
Rat
“The absence of toxicity was evaluated after repeated administrations in the rat according to treatment schedules mimicking a human vaccination scheme (i.e., 3 injections at monthly intervals).”
Species: DART
Not conducted
“Animal reproduction studies have not been conducted.”
Species: carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Surrogate used in
No surrogate; nonclinical data extrapolated from the HEXAVAC and PROCOMVAX combination vaccines
“The data from the HEXAVAC and PROCOMVAX studies can be extrapolated to the monovalent, thiomersal-free hepatitis B vaccine.”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Rabbit (four repeat-dose studies) and rat (one repeat-dose, DART, safety pharmacology); dog for MPL alone
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)
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