Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Rabbit (repeat-dose toxicity, DART) and rat (DART); mice for immunogenicity only
Nuvaxovid: which tox species, and why?
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Species
Rabbit for the adjuvanted vaccine; rats and rabbits for Matrix-M1 adjuvant studies
“A repeat-dose GLP-compliant study with SARS-CoV-2 rS in rabbits was performed, with or without the adjuvant Matrix-M1. In addition, 6 GLP-compliant repeated dose toxicity studies in rats and rabbits with other vaccines in combination with Matrix-M1, or Matrix-M1 alone, were provided, in which the toxicity of Matrix-M1 was evaluated.”
Why that species
Rat chosen for DART after a pilot study showed the adjuvanted vaccine is immunogenic in male and female rats
“A non-GLP pilot study in rats indicated that SARS-CoV-2 rS adjuvanted with Matrix-M1 is immunogenic in female and male rats following one and two immunisations.”
Surrogate molecule
No surrogate; clinical antigen tested with and without Matrix-M1 adjuvant
“A repeat-dose GLP-compliant study with SARS-CoV-2 rS in rabbits was performed, with or without the adjuvant Matrix-M1.”
Species: general tox
Rabbit (adjuvanted vaccine); rat and rabbit (Matrix-M1 adjuvant studies)
“A repeat-dose GLP-compliant study with SARS-CoV-2 rS in rabbits was performed, with or without the adjuvant Matrix-M1. In addition, 6 GLP-compliant repeated dose toxicity studies in rats and rabbits with other vaccines in combination with Matrix-M1, or Matrix-M1 alone, were provided, in which the toxicity of Matrix-M1 was evaluated.”
Species: DART
Rat (combined fertility, embryo-fetal and postnatal study, females dosed before mating and in gestation)
“A DART study in rats with SARS-CoV-2 rS + Matrix-M1 or Matrix- M1 alone (administered 27 and 13 days prior to cohabitation and on gestation day (GD) 7 and 15) has been performed.”
Species: carcinogenicity
Not conducted (WHO vaccine guidelines)
“No carcinogenicity studies have been performed with the SARS-CoV-2 rS vaccine and Matrix-M1 adjuvant in accordance with the WHO Guidelines on Non-clinical Evaluation of Vaccines (2005) and Guidelines on the Non-clinical Evaluation of Vaccine Adjuvants and Adjuvanted Vaccines (2014).”
Surrogate used in
No surrogate used; clinical antigen with Matrix-M1 and Matrix-M1 alone tested
“A DART study in rats with SARS-CoV-2 rS + Matrix-M1 or Matrix- M1 alone (administered 27 and 13 days prior to cohabitation and on gestation day (GD) 7 and 15) has been performed.”
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)
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
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