Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)In mice, AS01-adjuvanted RSVPreF3 induced CD4+/CD8+ T cells, neutralising antibodies and proinflammatory cytokines
PreHevbrio: which risks did reviewers probe?
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs
Immune & cytokine safety
Slight lymphoid hyperplasia in spleen and lymph nodes, an expected immunostimulatory effect
“There were no vaccine-related adverse gross or microscopic pathologic findings observed at terminal necropsy other than isolated incidence of slight discrete lymphoid hyperplasia in the spleens and lymph nodes of the vaccine treated rats, which represented an expected immunostimulatory property of the vaccine.”
Biodistribution & persistence
No pharmacokinetic studies; accepted by CHMP
“Pharmacokinetic studies were not performed with PreHevbri. This was considered acceptable by the CHMP.”
Modality-specific risk
Aluminium adjuvant injection-site reaction: mononuclear infiltration, myodegeneration and Al(OH)3 deposits
“The analysis of the injection site at four weeks showed essentially a mononuclear cell infiltration with signs of myodegeneration and depositions of Al(OH)3 in all groups.”
Anti-drug antibodies: animals
Rat seroconversion 100% (10 µg) and 70% (2 µg) in repeat-dose study, confirming immune response
“In the repeated dose toxicity study, 100% and 70% seroconversion were observed for the 10 µg and 2 µg HBsAg dose level, respectively, when administered IM on a 3-dose schedule (Days 0, 14 and 28).”
Anti-drug antibodies: patients
Intended response: seroprotection rate 91.4% vs 76.5% with Engerix-B
“The SPR was 91.4% (95% CI: 89.1, 93.3) in the PREHEVBRIO group and 76.5% (95% CI: 73.2, 79.5) in the ENGERIX-B group.”
Same question, other vaccines
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)No neurological, immunological or autoimmune adverse reactions in MPL-containing preclinical studies (FDA concurred)
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Transient neutrophil, monocyte, basophil and inflammatory-marker increases; spleen weight increase and lymphoid hyperplasia
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)Anti-HBs seroconversion in rabbits; rat dams and offspring exposed to high anti-HBs titres
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsTheoretical autoimmunity from cross-reactive antibodies, not readily studied in animals; left to clinical assessment
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsTransient spleen weight increase from immune stimulation; theoretical autoimmunity risk left to post-marketing
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNo autoimmune reactions, kidney or vascular lesions, or immune complex deposition in the rat repeat-dose study
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Serum IL-12p40 rose only 2-fold at ~20x the human CpG 1018 dose; no IL-12p40 or IFN-gamma increase at the 1x human dose
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Transient neutrophil and fibrinogen increases after dosing, back to pre-dose levels within three days
Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Matrix-M1: injection-site inflammation, reversible draining lymph node enlargement, raised CRP, fibrinogen and globulin (immune stimulation)
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Acute-phase response (CRP rise) indicating systemic inflammation, possibly linked to malaise, fatigue and nausea
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot stated in public reviews