No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines

- Vaccine reactogenicity can be misperceived as a greater risk than infectious disease.
- Public acceptance of side effects is reduced when infectious risks are perceived as low.
- Side effects are surprisingly consistent in three clinical studies of adjuvants.
- Alum works well as an adjuvant for HPV but not acellular pertussis vaccines.
- The pioneering adjuvant MPL should be considered for use in pertussis vaccines.

Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccine's reactogencicity are predictive of successful immunization outcomes. Recent clinical studies of pertussis and human papillomavirus vaccines adjuvanted with alum or the TLR4 agonist monophosphoryl lipid A can be used to advance understanding of the relationship between vaccine side effects and immunization outcomes.