Super Safe Adjuvant for Mucosal Vaccine


January 4, 2021

Phagocytosis of BoHA, and its cargo, by immune cells effectively activates the mucosal immune system

Key Word : Immunology, Small Molecule, Vaccine

Background / Context / Abstract:

Mucosal, such as oral and nasal vaccines are ideal not only for the invasive reason, but because they can induce mucosal immunity. Although several adjuvants for mucosal vaccines have been presented, most of them have toxicity or inflammatory side effects, which is undesirable for vaccination (eg. Cholera toxin B: CTB, heat-labile enterotoxin: LT).

Technology Overview:

BoHA is a non-toxic subcomponent of botulinum neurotoxin (BoNT). The mechanism by which BoNT crosses the intestinal epithelial barrier had previously remained unclear. The inventor, for the first time, discovered that BoHA acts as a carrier of toxin, which binds to and penetrates the M-cell of mucosa and bring the toxin into the lymph node, and leads to botulism. BoHA can also carry other molecules. Phagocytosis of BoHA, and it’s cargo, by immune cells effectively activates the mucosal immune system.


・BoHA alone has very low toxicity, and does not induce inflammatory cytokine.
・Nasal / Oral co-administration with antigen induces high IgA and IgG with minimal inflammatory response.
・BoHA can be produced by inexpensive recombinant E.coli system.

Further Details:

・In mouse (C57BL/6, BALB/c) influenza split vaccine immunization model, three time intranasal administration of antigen+BoHA 3 times every 2 weeks significantly induced IgG in serum and IgA in lung / nasal lavage fluid, although lesser than CTB.
・BoHA did not induce IL-6/TNF-alpha secretion from spleen cell of C57BL/6 mouse or affect LPS stimulated cytokine secretion.
・Mutation to eliminate E-cadherin binding function of BoHA did not reduce immunization effect.
・Partly published in journal, vaccination effect is in preparation.

Potential Applications / Potential Markets:

・Mucosal vaccine adjuvant

State of Development / Opportunity / Seeking:

・Available for exclusive and non-exclusive licensing
・Exclusive/non-exclusive evaluation for defined period (set up for options)
・Collaborative/supportive research

IP Status:

・WO2014/087849 (National phase US, EP and Issued: JP)
  NOTE: Fully assigned from Daiichi Sankyo Company Ltd.,
・WO2015/186678 (National phase JP, EP and Issued: US, TW)


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