The safety evaluation of adjuvants during vaccine development: The AS04 experience

An approach to local immunotoxicity induced by adjuvanted vaccines

“…Neutrophil depletion had no effect on the recruitment of other immune cells, including monocytes, macrophages and dendritic cells, and the specific antibody response was also unaffected in comparison with the control (non-neutrophildepleted) group [107]. Similarly, several other reports have demonstrated that adjuvanticity and adjuvant efficacy are not always associated with significant local inflammatory reactions [108][109][110][111][112][113]. Taken together, this evidence suggests that the recruitment of inflammatory cells may not be the key event in adjuvant-mediated immune enhancement, and additional investigation of the role of neutrophils in the induction of the immune response is needed [114].…”

Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine

“…They may increase the ability of antigens to activate signaling pathways to control the induction of innate and adaptive immunity, predominantly targeting APCs [6][7][8][9][10][11]. For over 70 years, aluminum salts (Alum) have been used as adjuvants in human vaccines [12,13]. They act as a depot for vaccine antigen components in order to enhance antigen uptake by APCs.…”

“…Mice (n = 5) were intramuscularly immunized twice at a 2-week interval with the indicated amount of antigen alone or together with adjuvant in 50 l PBS. Antibody titer: (a) IgG, (b) IgG1, (c) IgG2c were measured by ELISA [(1,4,7,10); antigen alone,(2,5,8,11); HBsAg Alum,(3,6,9,12); HBsAg Alum MPLA/HA].…”

Safety assessment of adjuvanted vaccines: Methodological considerations

“…[45][46][47] Clinical trials need to be appropriately designed in terms of sample size and choice of comparator. It is possible to comprehensively evaluate adverse events that occur at moderate to low frequency events in clinical trials.…”