Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not conducted for the vaccine (not required for vaccines)
Mosquirix: genotox, carcinogenicity and repro: done or skipped?
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)
Genotoxicity
Not conducted on the final vaccine; adjuvant system components tested instead
“Vaccines are not used in the long term and this reduces risk from consequences of genotoxicity. However, the genotoxic potential of the Adjuvant System and its components should be understood.”
Carcinogenicity
Not conducted (not required for vaccines, adjuvant systems or immunoenhancers per WHO/EMA guidance)
“According to the WHO Guidelines on Nonclinical Evaluation of Vaccines (WHO, 2005), the EMEA Note for Guidance on Preclinical Pharmacological and Toxicological testing of Vaccines (CPMP/SWP/465/95) and the Guideline on adjuvants in vaccines for human use (EMEA/CHMP/VEG/134716/2004), carcinogenicity studies are not required for final vaccine formulations, Adjuvants Systems and/or immunoenhancers.”
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
Not conducted: vaccine not intended for women of childbearing potential
“and developmental toxicity studies were not included in this Application since the RTS,S/ AS01E candidate vaccine containing, AS01E, MPL, QS-21 is not intended for administration to women of childbearing potential.”
Safety pharmacology
Three dedicated GLP studies: RTS,S/AS01B, AS01B and MPL
“Three dedicated safety pharmacology studies were performed with RTS,S/AS01B, AS01B and with MPL (Table 6) all conducted under GLP.”
Genotox: Ames
MPL negative in bacterial reverse mutation test
“MPL did not induce mutations in any of the five tester strains, when tested under the conditions employed in this study.”
Genotox: in vitro mammalian
MPL negative in CHO chromosome aberration assay
“MPL did not increase the proportion of cells with structural aberrations.”
Genotox: in vivo
AS01B negative in rat bone marrow micronucleus test, with bone marrow cell toxicity
“The conclusion of the applicant was that AS01B showed no evidence of causing micronuclei but did show evidence of causing bone marrow cell toxicity.”
Carcinogenicity model
Not conducted (not required per WHO/EMA vaccine guidance)
“According to the WHO Guidelines on Nonclinical Evaluation of Vaccines (WHO, 2005), the EMEA Note for Guidance on Preclinical Pharmacological and Toxicological testing of Vaccines (CPMP/SWP/465/95) and the Guideline on adjuvants in vaccines for human use (EMEA/CHMP/VEG/134716/2004), carcinogenicity studies are not required for final vaccine formulations, Adjuvants Systems and/or immunoenhancers.”
Carcinogenicity timing
Not required for vaccines, adjuvant systems or immunoenhancers (WHO/EMA guidance)
“According to the WHO Guidelines on Nonclinical Evaluation of Vaccines (WHO, 2005), the EMEA Note for Guidance on Preclinical Pharmacological and Toxicological testing of Vaccines (CPMP/SWP/465/95) and the Guideline on adjuvants in vaccines for human use (EMEA/CHMP/VEG/134716/2004), carcinogenicity studies are not required for final vaccine formulations, Adjuvants Systems and/or immunoenhancers.”
hERG / QT
AS01B in conscious dog: no relevant effect on QT/QTc or other ECG intervals over 72 hours
“AS01B administered intramuscularly, did not affect the health status and the body weight gain of the animals throughout the study period, and did not relevantly affect the arterial blood pressure, the heart rate and the duration of the RR and PR intervals, of the QRS complex and of the QT and QTc intervals, irrespective of the formula used for QT interval correction, during the 72-hour period following administration.”
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
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