Vaccine Safety Science

A tale of two (or three) aluminium adjuvants

A recent mini-spate of published papers on vaccine safety science, some good and some not so good, prompts me to revisit our contribution to the field. It all began with a burgeoning realisation that the great and the good of immunology and vaccine science had little if any understanding of how aluminium adjuvants work. As one might imagine, the manuscript was not popular with the field and it took a brave and forward thinking editor to see it published. The 200+ citations so far suggest that he was right to support our position. Subsequent research allowed us to begin to answer the question on how aluminium adjuvants work and, importantly, how they don’t work. I write about this subject extensively in my book a passage from which I have included below.

Recall that vaccines requiring an aluminium adjuvant do not work in the absence of the adjuvant. The antigen is not by itself sufficiently antigenic to initiate any form of effective immune response. Imagine the scene in the vaccine manufacturers’ research laboratory at the time when they are testing the ability of the antigen to elicit an antibody response. Every negative response is met with an increase in the amount of aluminium adjuvant added to the vaccine until an effective antibody titre is achieved. At no point does anyone question the amount of aluminium required to achieve the desired effect. There is no requirement to ask such a question. In spite of the obvious, that it is the aluminium adjuvant that is immunoreactive, the adjuvant is considered as benign in the process of development of the vaccine.

So, how do aluminium adjuvants work? We further addressed this question in our work on macrophages and we were able to show that these cells gorged upon aluminium adjuvant filling their cell body with packages of adjuvant. Critically they did this when exposed to very low concentrations of adjuvant. Immunoreactive cells, such as macrophages, capable of moving throughout the body, for example, capable of delivering adjuvant and antigen to lymph nodes, only required exposure to very low concentrations of aluminium adjuvant to be fully immuno-functional. We are talking about concentrations of aluminium adjuvant significantly lower, 10-100 times, than are actually used in vaccines. So, why do vaccine manufacturers use abominably high concentrations of aluminium adjuvants in vaccines?

A vaccine will only work if immunoreactive cells are attracted to the vaccine injection site. This signalling event requires activity at the injection site and the easiest way to achieve such reactivity and subsequent signalling is through toxicity. As I have said many times before, an aluminium adjuvant in a vaccine is an acute exposure to aluminium. The total concentration of aluminium at the injection site is sufficient to produce necrotic cell death, a subsequent inflammatory response (the red mark on your arm) and is the bugle cry that brings in the cavalry of myriad immunoresponsive cells. Different aluminium adjuvants produce different levels and perhaps manifestations of toxicity. Vaccine manufacturers are generally not that bothered about the toxicity of their vaccine, only whether or not it induces a sufficient antibody titre, though the nature of aluminium toxicity at the injection site may be the clue to serious adverse events that inevitably follow.