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
Shingrix: which risks did reviewers probe?
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Immune & cytokine safety
Acute-phase response (CRP rise) indicating systemic inflammation, possibly linked to malaise, fatigue and nausea
“These changes in CRP levels reflect an activation of the acute-phase response and indicate increasing levels of systemic inflammation, which potentially may be correlated with clinical adverse events such as malaise, fatigue, and nausea.”
Biodistribution & persistence
Adjuvant biodistribution only: QS-21 and MPL widely distributed, eliminated within 48-168 h
“Taken together, the biodistribution studies with QS-21 and MPL administered in solution have shown that QS-21 and MPL are widely distributed throughout the body and are eliminated within several hours (48-168 h).”
Modality-specific risk
Adjuvant QS-21: kidney and great-vessel malformations in rabbits, not rats, at doses well above clinical
“The final conclusion on the adjuvant component QS-21 is that it potentially induces treatment related adverse findings including kidney and great blood vessel malformations in rabbits but not in rats, at doses considered sufficiently in excess over the therapeutic dose to raise any concern.”
Anti-drug antibodies: animals
All vaccine-treated rabbits seroconverted (anti-gE ELISA), confirming exposure
“All gE/AS01B treated animals seroconverted as assessed by gE ELISA.”
Anti-drug antibodies: patients
Intended response: anti-gE vaccine response rate 96.5% one month after the second dose (0, 6-month schedule)
“The co-primary objectives for the 0, 6-month schedule were met: (1) the Vaccine Response Rate at one month after the second dose was 96.5% (97.5% CI: 90.4 to 99.2), with LL of the 97.5% CI ≥60%;”
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)
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
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot stated in public reviews