A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin-based adjuvants

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

“…However, the development of effective mucosal vaccines is still jeopardized by the poor immunological properties of nonreplicating antigens and the lack of efficient delivery systems and mucosal adjuvants (14). To date the most effective mucosal adjuvants are CT and LT and their genetically detoxified mutant versions, which are used as vaccine carriers and immunomodulators (38).…”

A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection

“…3 to raise mucosal immune responses due to the concern that they could result in localization to the CNS (26). Instead, generation of mucosal immune responses usually requires the inclusion of potentially toxic adjuvants delivered with a protein component of the vaccine (27)(28)(29). Development of immune responses to the viral vector raises concerns over widespread and repeated use of viral vectors (4,30).…”

Is the choice of vaccine adjuvant critical for long-term memory development?

“…This is a promising novel vaccine adjuvant, which carries the ADP-ribosylating CTA1-moiety of CT, while the receptor-binding B subunit has been replaced by a dimer of the D fragment from Staphylococcus aureus protein A [31]. Hence, CTA1-DD does not bind GM1 ganglioside receptors present on all nucleated cells and does not interact with the central nervous tissues, as has been observed for CT and LT following intranasal administration, which was also the reason [32,33] for taking an LT-adjuvanted intranasal influenza vaccine off the market a few years ago [34]. CTA1-DD has been found to host a broad range of adjuvant functions, greatly augmenting cell-mediated and humoral immune responses to admixed antigen [35].…”