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Precedia/Protein and VLP vaccines/Arexvy/Risks

Arexvy: which risks did reviewers probe?

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Check my plan vs. these
Immune & cytokine safety
In mice, AS01-adjuvanted RSVPreF3 induced CD4+/CD8+ T cells, neutralising antibodies and proinflammatory cytokines
“In combination with especially AS01B, RSVPreF3 induced F-specific CD4+ and CD8+ T cell responses and RSV-specific neutralising antibody titres after the second and third vaccination and induced proinflammatory cytokines as measured after the first and second vaccination.”
✓ VerifiedEMA assessment report, p. 30Source ↗
Biodistribution & persistence
No PK/ADME or new biodistribution studies; AS01 not a novel adjuvant (registered in Shingrix)
“No dedicated PK or ADME studies for RSVPreF3 OA are performed. This is endorsed. The adjuvant system AS01 is not a novel adjuvant, since several products using the adjuvant system have already been registered (a.o., Shingrix, using AS01B).”
✓ VerifiedEMA assessment report, p. 31Source ↗
Modality-specific risk
Adjuvant-driven local reactogenicity: injection-site myofiber degeneration/necrosis and inflammation, more severe with adjuvant
“Local effects at the injection site included minimal to slight myofiber degeneration/necrosis and minimal to moderate mixed inflammatory cell infiltrates, and were in general, more severe in the adjuvanted RSVPreF3 group.”
✓ VerifiedEMA assessment report, p. 32Source ↗
Anti-drug antibodies: animals
Anti-RSVPreF3 IgG in 80-90% of females and all males given RSVPreF3 with or without AS01B; confirms exposure
“Levels of anti-RSVPreF3 IgG antibodies were increased (measured at Day 32 and 57) in 80% of females and all males administered RSVPreF3 and in 80-90% of females and all males administered RSVPreF3 adjuvanted with AS01B in the first study.”
✓ VerifiedEMA assessment report, p. 32Source ↗
Anti-drug antibodies: patients
Intended immune response: ~10-fold RSV-A and ~8-fold RSV-B neutralising titre rise at 1 month
“After vaccination a substantial and consistent immune response was observed, with at 1-month postvaccination a ~10-fold increase in RSV-A neutralising antibody titres, an ~8-fold increase in RSV-B neutralising antibody titres, and a ~12-fold increase in binding antibody titres being observed across studies.”
✓ VerifiedEMA assessment report, p. 101Source ↗

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 VLPs
Theoretical 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 VLPs
Transient spleen weight increase from immune stimulation; theoretical autoimmunity risk left to post-marketing

HBVaxPro

hepatitis B vaccine (rDNA) · HBsAg VLPs
No 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 VLPs
Slight 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 HA
Not stated in public reviews

Summary across all 13 vaccines →