A Fusion Protein Consisting of the Vaccine Adjuvant Monophosphoryl Lipid A and the Allergen Ovalbumin Boosts Allergen-Specific Th1,Th2,and Th17 Responses in Vitro

Background. the detoxified tlr4-ligand monophosphoryl lipid a (mpla) is the first approved tlr-agonist used as adjuvant in licensed vaccines but has not yet been explored as part of conjugated vaccines. objective. to investigate the immune-modulating properties of a fusion protein consisting of mpla and ovalbumin (mpla: ova). results. mpla and ova were chemically coupled by stable carbamate linkage. mpla: ova was highly pure without detectable product-related impurities by either noncoupled mpla or ova. light scattering analysis revealed mpla: ova to be aggregated. stimulation of mdc and mdc: do11.10 cd4+ tc cocultures showed a stronger activation of both mdc and ova-specific do11.10 cd4+ tc by mpla: ova compared to the mixture of both components. mpla: ova induced both strong proinflammatory (il-1β,il-6,and tnf-α) and anti-inflammatory (il-10) cytokine responses from mdcs while also boosting allergen-specific th1,th2,and th17 cytokine secretion. conclusion. conjugation of mpla and antigen enhanced the immune response compared to the mixture of both components. due to the nonbiased boost of ova-specific th2 and th17 responses while also inducing th1 responses,this fusion protein may not be a suitable vaccine candidate for allergy treatment but may hold potential for the treatment of other diseases that require a strong stimulation of the host's immune system (e.g.,cancer). © 2016 stefan schülke et al.