A systematic assessment of the relationship between synthetic surfactants and mucosal adjuvanticity

Intranasal immunization with surfactants as vaccine adjuvants enhances protective immunity against invasive mucosal pathogens. However, the effects of surfactants and their adjuvanticity on mucosal immune responses remain unclear. Comparison of the mucosal adjuvanticity of 20 water-soluble surfactants from the four classes based upon the polarity composition of the hydrophilic headgroup revealed that the order of mucosal adjuvanticity was as follows: amphoteric > nonionic > cationic > anionic. Within the same class, each surfactant displayed different adjuvanticity values. Analysis of the diameter and ζ-potential of amphoteric surfactant-OVA complexes and their surface physicochemical properties revealed that the diameter was approximately 100 nm, which is considered suitable for immune induction, and that the ζ-potential of the anionic surfactant-OVA complexes was exceedingly negative. The increase in the number of carbon atoms in the hydrophobic tailgroups of the amphoteric surfactant resulted in an increase in the OVA-specific Ab titers. Our findings demonstrate that amphoteric surfactants exhibit potent mucosal adjuvanticity and highlight the importance of the number of carbon atoms in the tailgroups and the diameter and ζ-potential of the complexes when designing mucosal adjuvants.