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
Heplisav-B: which risks did reviewers probe?
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
Immune & cytokine safety
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
“The 300 mcg 1018 ISS + HBsAg dose (approximately 20 times the human dose) induced only a 2-fold increase in IL-12p40 levels over baseline, and the 15 mcg 1018 ISS + HBsAg dose (a 1 X human dose) did not induce an increase in either IL-12p40 or IFN-g levels after the first or last injection.”
Biodistribution & persistence
Rapid plasma decline; PS-ODN binds plasma proteins (95%) and distributes to kidney (up to 20% of dose), liver and spleen
“According to published data the rapid decline is due to initial low affinity binding to plasma proteins (95%) and to significant distribution to kidney (up to 20 % of the dose), liver, and to a minor extent spleen.”
Modality-specific risk
Oligonucleotide class effect: CpG 1018 kidney accumulation in rats with non-reversible tubular degeneration and interstitial inflammation
“Most of the observed changes were reversible, except for accumulation of the CpG 1018 in the kidneys in male rats of all groups as well as female rats receiving 2.5 and 12.5 mg/kg/week which led to minimal to moderate tubular degeneration and minimal to moderate chronic interstitial inflammation in a dose dependent manner.”
Anti-drug antibodies: animals
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Anti-drug antibodies: patients
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
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
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