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
Fendrix: which risks did reviewers probe?
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
Immune & cytokine safety
Anti-HBs seroconversion in rabbits; rat dams and offspring exposed to high anti-HBs titres
“Furthermore, rat dams and offspring were shown to be exposed to high titres of circulating anti-HBs antibodies during the reproductive toxicity study.”
Biodistribution & persistence
No distribution or excretion data for vaccine or AS04C; assumed to follow unadsorbed aluminium particle disposition
“Neither distribution nor excretion data are available for the final HB-AS04C vaccine or the AS04C adjuvant. However, the applicant assumes that aluminium salt particles containing adsorbed materials follow the same distribution and elimination as for unadsorbed aluminium particles.”
Modality-specific risk
Adjuvant (MPL) immunostimulation: possible autoimmune disease to be watched after approval
“attention to autoimmune disease events will have to be paid in the post-marketing phase.”
Anti-drug antibodies: animals
Seroconversion in vaccine-treated rabbits (not controls or adjuvant-only), confirming exposure; high anti-HBs in rat dams and offspring
“Serological analysis demonstrated that unlike controls or adjuvant receiving animals, vaccine-treated rabbits showed a seroconversion in the repeat-dose toxicity study.”
Anti-drug antibodies: patients
Intended response: seroprotection 90.9% at Month 7 in (pre-)haemodialysis patients vs 84.4% with double-dose comparator
“In studies HBV-MPL 032 and 042 in (pre-) haemodialysis patients, primary vaccination with Fendrix elicited a seroprotection of 90.9% at Month 7 as compared to 84.4% with a double dose of a commercially available HepB vaccine, which is standard in these patients.”
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
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)
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsSlight lymphoid hyperplasia in spleen and lymph nodes, an expected immunostimulatory effect
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