Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Immunogenicity of RSVPreF3 with or without AS01 in naive mice (neutralising antibodies, CD4+/CD8+ T cells); no challenge model
Cyfendus: animal efficacy model or human cells?
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)
Efficacy evidence
Guinea pig and cynomolgus macaque lethal aerosolized B. anthracis spore challenge after two IM vaccinations
“Efficacy studies for CYFENDUS were conducted in guinea pigs and cynomolgus macaques. Animals received two intramuscular vaccinations two weeks apart with various dilutions of CYFENDUS and were challenged with a lethal dose of aerosolized B. anthracis spores on Day 28 or 70.”
Why that model
CpG 7909 activity significantly weaker in rabbits, so a guinea pig inhalational anthrax model was developed
“The activity of the CpG 7909 adjuvant has been observed to be significantly weaker in rabbits; therefore, to provide a suitable additional animal to demonstrate the effectiveness of CYFENDUS, the applicant developed and used a guinea pig model of inhalational anthrax.”
Reviewer's view of the efficacy data
FDA identified no deficiencies with the nonclinical animal studies
“No deficiencies were identified with the nonclinical animal studies”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Immunogenicity in mice and rhesus monkeys (AS04 superior to aluminium alone); no protection model
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)Immunogenicity in mice: HBsAg with AS04C more immunogenic than with alum
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HAMouse immunogenicity (HAI and neutralizing antibodies) with monovalent rH3 and trivalent RIV3; no challenge studies
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsImmunogenicity in rhesus macaques, chimpanzees and African green monkeys; neutralising antibodies; no HPV challenge model
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsImmunogenicity in rhesus macaques (non-GLP): antibodies to all 9 HPV types; no protection model
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsC3H mouse potency (ED50) testing versus the licensed thiomersal-containing vaccine
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Anti-HBsAg immunogenicity of the adjuvanted vaccine in mice, rats and baboons
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Immunogenicity in mice and monkeys (3 IM doses, days 0, 14, 28)
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)SARS-CoV-2 live-virus challenge in mice, hamsters, cynomolgus and rhesus macaques
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsImmunogenicity in mice and rats; no challenge model
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Immunogenicity (cellular and humoral anti-gE) in mice