Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Cervarix: genotox, carcinogenicity and repro: done or skipped?
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
Genotoxicity
Vaccine not tested; MPL adjuvant negative in Ames, CHO clastogenicity and in vivo micronucleus
“The in vitro mutagenicity (Ames) and clastogenicity (CHO cells) tests, and in vivo micronucleus assay demonstrated no genotoxic potential of the MPL adjuvant.”
Carcinogenicity
Not conducted; accepted as the vaccine is L1 protein without HPV oncoproteins
“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.”
Instead of 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.
Instead of genotoxicity
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.
DRG histopathology
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.
Reproductive & developmental
Rat combined fertility, embryo-fetal and pre/postnatal study with vaccine and AS04: no effects
“The reproductive toxicity study in CD rats did not show any effects of vaccination or AS04 administration on fertility, embryofoetal development and pre- and post-natal development.”
Safety pharmacology
Dedicated studies: vaccine in anaesthetised rats, MPL in dogs; no cardiovascular or respiratory effects
“Safety pharmacology studies were performed on HPV-16/18 L1 VLP AS04 in rats and on MPL in dogs.”
Genotox: Ames
MPL adjuvant: Ames negative (vaccine not tested)
“The in vitro mutagenicity (Ames) and clastogenicity (CHO cells) tests, and in vivo micronucleus assay demonstrated no genotoxic potential of the MPL adjuvant.”
Genotox: in vitro mammalian
MPL adjuvant: chromosomal aberration (CHO cells) negative
“The in vitro mutagenicity (Ames) and clastogenicity (CHO cells) tests, and in vivo micronucleus assay demonstrated no genotoxic potential of the MPL adjuvant.”
Genotox: in vivo
MPL adjuvant: in vivo micronucleus negative
“The in vitro mutagenicity (Ames) and clastogenicity (CHO cells) tests, and in vivo micronucleus assay demonstrated no genotoxic potential of the MPL adjuvant.”
Carcinogenicity model
Not conducted (L1 protein vaccine without HPV oncoproteins)
“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.”
Carcinogenicity timing
Not required (L1 protein vaccine without HPV oncoproteins)
“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.”
hERG / QT
No effects on blood pressure, heart rate, ECG or respiration in anaesthetised rats
“Intramuscular administration of 0.1ml/animal of the HPV-16/18 L1 VLP AS04 vaccine did not produce any treatment-related effects on blood pressure, heart rate, ECG (lead II) or respiration depth and rate”
Same question, other vaccines
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Not conducted
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)MPL only: negative in Ames and CHO clastogenicity tests; vaccine not tested
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot conducted (not normally required for viral vaccines; no adjuvant)
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsNot conducted (CPMP/SWP/465/95 vaccine guidance)
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsNot conducted (vaccine guidance; CHMP agreed)
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)CpG adjuvant negative in Ames, in vitro chromosome aberration and in vivo mouse micronucleus tests
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Not conducted on the final vaccine; adjuvant system components tested instead
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Matrix-M1 adjuvant negative in GLP Ames and in vitro CHO micronucleus assays; in vivo testing judged unnecessary
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsNot conducted (in line with applicable guidelines)
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Not conducted on the final vaccine formulation (considered acceptable)
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews