Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Australia: Study 2019nCoV-101 Part 1, started May 2020
Flublok: what was done before first-in-human, and what came after?
influenza vaccine, recombinant hemagglutinin · Influenza HA
Before first-in-human
First-in-human: where
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.
Repeat-dose tox before first-in-human
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.
First-in-human starting dose
Antigen content of quadrivalent product matched licensed trivalent vaccine plus a second B strain; no separate dose-finding
“The quantity of each HA antigen and excipients of RIV4 was equivalent to that of the US licensed trivalent recombinant influenza vaccine manufactured by PSC with the addition of the second B strain.”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
Rat, five weekly SC injections of RIV3; recovery phase not stated
“The pivotal repeat-dose toxicity study was conducted with the SC route. Results showed that five weekly SC injections with RIV3 were locally and systemically well tolerated in rats.”
Pivotal GLP studies
GLP rat repeat-dose study, five weekly SC injections of RIV3; rat IM DART; single-dose, local tolerance studies
“The pivotal repeat-dose toxicity study was conducted with the SC route. Results showed that five weekly SC injections with RIV3 were locally and systemically well tolerated in rats.”
DART package
Species: DART
Rat (fertility, embryo-fetal and early postnatal development, combined study)
“In DART study conducted in female rats, three IM injections (31 and 12 days before mating and on Gestation Day 6) of RIV3 did not induce maternal toxicity, and there were no adverse effects on mating performance or fertility, embryo-foetal development (including an evaluation of teratogenicity) and an early post-natal development.”
Reproductive & developmental
Rat fertility, embryo-fetal and early postnatal study (three IM doses, pre-mating and GD6): no adverse effects
“In DART study conducted in female rats, three IM injections (31 and 12 days before mating and on Gestation Day 6) of RIV3 did not induce maternal toxicity, and there were no adverse effects on mating performance or fertility, embryo-foetal development (including an evaluation of teratogenicity) and an early post-natal development.”
PPND / ePPND: when
Rat reproductive study with pre- and postnatal phase completed; final report reviewed for the original licence
“Reproductive toxicity study for FluBLOk, recombinant trivalent influenza vaccine: final report, review memorandum”
Carcinogenicity
Species: carcinogenicity
Not conducted
“No genotoxicity and carcinogenicity studies were carried out in line with relevant guidelines. Studies evaluating genotoxicity and carcinogenicity are normally not required for viral vaccines.”
Carcinogenicity model
Not conducted (not normally required for viral vaccines; no adjuvant or novel excipients)
“Studies evaluating genotoxicity and carcinogenicity are normally not required for viral vaccines. Since no adjuvants or novel excipients are used in this product absence of those studies is considered acceptable.”
Carcinogenicity timing
Not required: viral vaccine without adjuvant or novel excipients
“Studies evaluating genotoxicity and carcinogenicity are normally not required for viral vaccines. Since no adjuvants or novel excipients are used in this product absence of those studies is considered acceptable.”
Same question, other vaccines
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsIsrael, Thailand and Singapore: legacy dose-ranging studies, one with a first-in-human part up to 20 µg
Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not stated in public reviews
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Not stated in public reviews
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Not stated in public reviews
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)Not stated in public reviews
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsNot stated in public reviews
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsNot stated in public reviews
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Not stated in public reviews
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Not stated in public reviews
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Not stated in public reviews