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Cyfendus: which tox species, and why?

anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)
Species
Rat only
“All these GLP-compliant toxicology studies were performed in rats.”
✓ VerifiedFDA toxicology review, p. 4Source ↗
Why that species
Widely used toxicology species; rats responded to the vaccine and CpG 7909, confirmed by immunogenicity in each study
“The rat model was chosen for the safety evaluation of AV7909 as it is a widely used species for toxicology studies and rats were shown to respond appropriately to AV7909 and its component, CPG 7909, as confirmed by immunogenicity assessments conducted in each of the studies.”
✓ VerifiedFDA toxicology review, p. 4Source ↗
Surrogate molecule
No surrogate; the clinical vaccine and CpG 7909 adjuvant alone were tested side by side
“Test article-related findings were observed in the adjuvant alone (CPG 7909) group as well as the Anthrax Vaccine Adsorbed (AVA), adjuvanted group with similar frequency and similar severity, which suggests that the findings were mostly induced by the adjuvant.”
✓ VerifiedFDA toxicology review, p. 4Source ↗
Species: general tox
Rat only
“All these GLP-compliant toxicology studies were performed in rats.”
✓ VerifiedFDA toxicology review, p. 4Source ↗
Species: DART
Female rat (pre/postnatal study with embryo-fetal phase, full human dose 0.5 mL)
“In a pre- and post-natal developmental study with an embryo-fetal development toxicity phase performed in female rats, a full human dose (0.5 mL) of CYFENDUS was administered by intramuscular injection on three occasions: 14 days prior to start of cohabitation, on the day of cohabitation, and on Gestation Day 7.”
✓ VerifiedUS package insert, p. 8Source ↗
Species: carcinogenicity
Not conducted
“CYFENDUS has not been evaluated for carcinogenicity, mutagenic potential, or male infertility in animals.”
✓ VerifiedUS package insert, p. 9Source ↗
Surrogate used in
No surrogate used; CYFENDUS itself dosed in rats
“The applicant conducted a single-dose acute toxicity study, a repeat-dose safety toxicity study, a pre- and post-natal developmental and reproductive toxicity (DART) study, as well as a juvenile repeat-dose toxicology study. All these GLP-compliant toxicology studies were performed in rats, and animals were dosed with CYFENDUS via IM injection, the intended route for human use.”
✓ VerifiedFDA summary basis for approval, p. 15Source ↗

Same question, other vaccines

Arexvy

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Rabbit (repeat-dose toxicity, DART) and rat (DART); mice for immunogenicity only

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

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 HA
Rat 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 VLPs
Mouse (repeat-dose), mouse and rat (single-dose), rat (DART), rabbit (local tolerance)

Gardasil 9

human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs
Rat only (repeat-dose, fertility/embryo-foetal and postnatal studies)

HBVaxPro

hepatitis B vaccine (rDNA) · HBsAg VLPs
Rat (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

Nuvaxovid

COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Rabbit for the adjuvanted vaccine; rats and rabbits for Matrix-M1 adjuvant studies

PreHevbrio

hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs
Rat only

Shingrix

zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Rat and rabbit

Summary across all 13 vaccines →