Physico-chemical properties of aluminum adjuvants in vaccines: Implications for toxicological evaluation.

[Display omitted] • Al oxyhydroxide and Al hydroxyphosphate have different physico-chemical properties: a key role on the biological effects. • The charges of Al oxyhydroxide and Al hydroxyphosphate are not modified by the antigen in vaccines except in the case of Infanrix Hexa®. • The mixing between Al oxyhydroxide and Al hydroxyphosphate does not occur at the elementary particle level in vaccine. • The dilution of vaccines or adjuvants leads to a decrease of the size of particles, which can have an impact on the induced cellular mechanisms. Aluminum salts have been used as adjuvants in human vaccines since 1932. The most used adjuvants are Al oxyhydroxide (AlOOH) and Al hydroxyphosphate (AlOHPO 4). Al adjuvants have different physico-chemical properties. The differences in these properties are not well documented and not considered by the Food and Drug Administration (FDA), though they can largely influence biological effects of the adjuvants which are particulate components. In this study, different physico-chemical properties including the shape, size and charge of particles have been evaluated under different conditions in three Al adjuvants containing-vaccines and two corresponding commercial adjuvants suspensions. The results showed that the two Al adjuvants have different shapes, sizes and charges but both form aggregates. In addition, a clear effect of dilution on the size of the aggregates was observed. Moreover, different sizes of Al particles were measured for both Al oxyhydroxide adjuvant alone or in the vaccine, at identical concentrations, displaying the impact of adsorbed proteins on the size of aggregates in the case of the vaccine. Taken together, this paper suggests the importance to evaluate, before any biological and especially toxicological impact study, the whole physico-chemical properties of Al particle without restricting to the sole evaluation of the injected concentration. Furthermore, any modification of these mentioned parameters during manipulation, before animal or cell exposure, should be considered. In a more global way, the fixed "safe dose" of Al adjuvants should be specific for each type of Al adjuvant independently or for a mix of the two compounds, due to their different properties. [ABSTRACT FROM AUTHOR]