Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines

Safety assessment of adjuvanted vaccines: Methodological considerations

“…Licensed adjuvanted vaccines have been shown to have clinically acceptable benefitrisk profiles, and concerns that adjuvanted vaccines may be associated with an increase in autoimmune disease have been unfounded. 77,78 The safety evaluation of an adjuvanted vaccine is ultimately based on the final vaccine (antigen and adjuvant). Collaborations between manufacturers and regulatory authorities aim to develop safety evaluation programs specific to a particular vaccine or population.…”

Update on Human Papillomavirus (HPV) Vaccines

“…Over 40 000 doses of AS04 have been administered in trials of these two vaccine products, and an additional 19 000 doses have been administered in the conduct of the bivalent HPV vaccine trial. (79,80) The vaccine formulation also includes 4.4 mg sodium chloride, 623 µg sodium dihydrogen phosphate dehydrate, and water for injections. (82) and FUTURE II (84) Efficacy of HPV4 in females >26 years of age Efficacy of HPV4 in females 24 to 45 years of age (n=3819) was studied in a randomized, double blind, placebo controlled trial at 38 international sites, from which 2.2 year (of four year) follow-up data is available.…”

“…(132) Results of three pooled studies to examine adverse events related to Cervarix™ or AS04 adjuvanted vaccine are now available. (80,146,147) These studies were designed to evaluate risk of serious adverse events (SAE) (146) , medically significant conditions (MSC) (146) , new onset chronic disease (NOCD), (146) new onset autoimmune disease (NOAD) (80,146) , and adverse pregnancy outcomes. (146,147) Table 14 provides incidence of adverse events in Cervarix™ recipients >9 years of age.…”

“…As Cervarix™ employs a new adjuvant, one pooled study extensively examined the risk of developing autoimmune disease. (80) The analysis examined recipients of Cervarix™ (n=39 160) or AS04 containing vaccines (n=68 512). The length of follow-up for vaccinees varied with trial protocol.…”

TLR, NLR Agonists, and Other Immune Modulators as Infectious Disease Vaccine Adjuvants

“…Since their discovery, it has been established that TLRs play important roles in recognising specific microbial components derived from pathogens, including bacteria, fungi, protozoa and viruses. To date, ten functional TLRs have study has report a good safety profile for the AS04 adjuvant in over 68,000 individuals [13].…”