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
Gardasil: which risks did reviewers probe?
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
Immune & cytokine safety
Theoretical autoimmunity from cross-reactive antibodies, not readily studied in animals; left to clinical assessment
“Theoretically, the vaccine could give rise to antibodies, which cross-react to self-structures, resulting in autoimmune events. Such possibility is not readily studied in experimental animal models, but can only be studied in the clinical situation.”
Biodistribution & persistence
ADME studies not performed (vaccine guidance)
“Experimental studies to demonstrate absorption, distribution, metabolism, and excretion of the active ingredients in Gardasil have not been performed for any of the component viruses. This is in line with Note for guidance on preclinical pharmacological and toxicological testing of vaccines (CPMP/SWP/465/95).”
Modality-specific risk
Injection-site reactogenicity: minimal irritation in rabbits, similar to aluminium adjuvant placebo
“Intramuscular administration of Gardasil caused minimal irritation at injection site and the changes observed were similar in severity to those produced by the injection of the Merck aluminium adjuvant as placebo control.”
Anti-drug antibodies: animals
All rats mounted antibody responses to all 4 HPV VLP types, confirming exposure
“There were no deaths or treatment-related physical signs during the study. All animals mounted specific antibody responses to all 4 HPV VLPs.”
Anti-drug antibodies: patients
Monovalent precursor vaccine: 90-100% of subjects reached the pre-specified cRIA level 4 weeks post dose 3
“The vaccine proved immunogenic with 90-100% of subjects reaching the pre-specified cRIA level of >200 mMU/ml 4 weeks postdose 3.”
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 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