Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Nuvaxovid: genotox, carcinogenicity and repro: done or skipped?
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Genotoxicity
Matrix-M1 adjuvant negative in GLP Ames and in vitro CHO micronucleus assays; in vivo testing judged unnecessary
“The confirmatory GLP-compliant bacterial reverse mutation assay and Mammalian Cell Micronucleus assay in CHO Cells with Matrix-M1 confirmed the absence of any indication for a genotoxic potential of Matrix-M1. Further in vivo studies were therefore not considered necessary.”
Carcinogenicity
Not conducted (WHO vaccine and adjuvanted 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).”
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 DART (dosing before mating and in gestation): no effects on reproduction, embryo-fetal or postnatal development to day 21
“The DART study confirmed that SARS-CoV-2 rS + Matrix-M1 or Matrix-M1 does not affect reproductive or developmental parameters and no adverse findings on pregnancy/lactation, or development of the embryo/foetus and offspring through post-natal Day 21 were identified.”
Safety pharmacology
Not conducted (WHO vaccine guideline); physiological functions assessed within the rabbit repeat-dose study
“Safety pharmacology studies were not conducted with SARS-CoV-2 rS with Matrix-M1 adjuvant vaccine, which is in line with the recommendation of the WHO Guidelines on Non-clinical Evaluation of Vaccines (2005), also given the availability of supporting non-clinical and clinical data, which indicated that the vaccine did not affect physiological functions other than those of the immune system.”
Genotox: Ames
Matrix-M1: GLP bacterial reverse mutation assay negative
“The confirmatory GLP-compliant bacterial reverse mutation assay and Mammalian Cell Micronucleus assay in CHO Cells with Matrix-M1 confirmed the absence of any indication for a genotoxic potential of Matrix-M1. Further in vivo studies were therefore not considered necessary.”
Genotox: in vitro mammalian
Matrix-M1: GLP micronucleus assay in CHO cells negative
“The confirmatory GLP-compliant bacterial reverse mutation assay and Mammalian Cell Micronucleus assay in CHO Cells with Matrix-M1 confirmed the absence of any indication for a genotoxic potential of Matrix-M1. Further in vivo studies were therefore not considered necessary.”
Genotox: in vivo
Not conducted (judged unnecessary after negative in vitro results)
“The confirmatory GLP-compliant bacterial reverse mutation assay and Mammalian Cell Micronucleus assay in CHO Cells with Matrix-M1 confirmed the absence of any indication for a genotoxic potential of Matrix-M1. Further in vivo studies were therefore not considered necessary.”
Carcinogenicity model
Not conducted (WHO vaccine and adjuvant 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).”
Carcinogenicity timing
Not required under WHO vaccine and adjuvanted 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).”
hERG / QT
Not conducted; no effects on physiological functions in the repeat-dose study
“Safety pharmacology studies were not conducted with SARS-CoV-2 rS with Matrix-M1 adjuvant vaccine, which is in line with the recommendation of the WHO Guidelines on Non-clinical Evaluation of Vaccines (2005), also given the availability of supporting non-clinical and clinical data, which indicated that the vaccine did not affect physiological functions other than those of the immune system.”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Vaccine not tested; MPL adjuvant negative in Ames, CHO clastogenicity and in vivo micronucleus
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
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