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
Arexvy: animal efficacy model or human cells?
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Efficacy evidence
Immunogenicity of RSVPreF3 with or without AS01 in naive mice (neutralising antibodies, CD4+/CD8+ T cells); no challenge model
“The Applicant has submitted three primary PD studies to characterise the immunogenicity of the PreF3-AS01E vaccine in mice and two immuno-characterization studies.”
Why that model
No animal model mimics the non-naive elderly population and its sensitivity to RSV disease
“The Applicant has thoroughly explained that the non-clinical studies are only intended to show immunogenicity and not to evaluate vaccine efficacy, because a good animal model that can mimic the intended human non-naïve elderly target population and the sensitivity to RSV-related disease upon infection is not present.”
Reviewer's view of the efficacy data
Proof-of-concept immunogenicity only; clinical relevance doubtful because murine antigen doses were very low
“However, the clinical relevance of the observed immune responses and the corresponding conclusions (including selection of the antigen type and adjuvant system) is doubtful because the used antigen doses used in the murine studies are very low (compared to the doses used in the rabbit tox study and in clinical studies)”
Same question, other vaccines
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Guinea pig and cynomolgus macaque lethal aerosolized B. anthracis spore challenge after two IM vaccinations
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