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
Cervarix: which risks did reviewers probe?
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
Immune & cytokine safety
No neurological, immunological or autoimmune adverse reactions in MPL-containing preclinical studies (FDA concurred)
“GSK’s 3rd table in their response lists the preclinical studies conducted with vaccine formulations containing MPL. GSK concluded that none of these studies show evidence of adverse neurological, immunological or autoimmune-based (AID) reactions.”
Biodistribution & persistence
Radiolabelled MPL in rat widely distributed (fat, spleen), likely eliminated via expired air; no vaccine ADME
“In conclusion the pharmacokinetic studies conducted in rats have shown that MPL-related material is widely distributed throughout the body, notably to the fat and spleen, and is then likely eliminated mainly via the expired air, with only low levels of radioactivity remaining in the carcass.”
Modality-specific risk
TLR4-agonist adjuvant (AS04/MPL): strong local inflammatory reaction at the injection site, amplified by up to 3x human dose
“This local effect is most likely the sign of the strong adjuvant effect induced by AS04. Furthermore, up to three times the full human dosage was used in the rabbit studies, probably amplifying this local reaction.”
Anti-drug antibodies: animals
Immune response in vaccinated rats; antibodies transferred to offspring in gestation and lactation
“An immune response to the vaccine was observed, and antibodies were transferred to the offspring during gestation and also during lactation.”
Anti-drug antibodies: patients
99.9% of initially seronegative subjects seroconverted to HPV 16 and 18 one month after the third dose
“In clinical trials assessing immunogenicity, 99.9% of initially seronegative subjects had seroconverted to both HPV types 16 and 18 one month after the third dose.”
Same question, other vaccines
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
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