The Study Of GM1-ganglioside Binding Peptides On Vaccine Transdermal Delivery

Vaccination is the most effective way to prevent infectious diseases,but there are no effective vaccine formulations available for transdermal delivery.And the adjuvant utilized in current vaccines often causes toxic side effects.From previous studies,we learned that the B subunit of cholera toxin(CT)can bind to GM1-ganglioside receptor on the cell membrane,which plays an essential role on the antigenicity and adjuvanticity of CT.What's more,the cell-penetraing peptides are more and more widely applied in drug delivery systems.Therefore,we hypothesize that the GM1 receptor-binding peptides(GMl-bps)may be employed as a molecular carrier for antigen and drug delivery.They may improve the efficiency of antigen presentation and help drugs through the cell membrane.The following studies have been carried out to testify the hypothesis.Firstly,two peptides,DP and VP were chosen from GM1-bp library and covalently-conjugated with ovalbumin,result in OVA-DP and OVA-VP.In cell-uptake experiments,macrophages prone to uptake OVA-DP more than OVA,OVA-VP,OVA mixed with DP and OVA mixed with VP at both 37 ? and 4? Correspondingly,vaccination using OVA-DP in mice induced significantly higher antibody titers than that of OVA,indicating that DP is an effective molecular antigen carrier and adjuvant with low toxicity.It can enhance antigen-uptake and antigen-presentation,thus the resulted antibody response when conjugated with the antigen.To get more optimal adjuvant,DP is combined with branched polyethyleneimine,a potent adjuvant with high toxicity.It was found that the group of PEI mixed with DP significantly improved the transfection efficiency as compared with PEI and PEI-DP.Vaccination with OVA using PEI+DP as adjuvant also induced higher antibody titers than using PEI or PEI-DP,which was at the similar level as the group using Freud'd incomplete adjuvant.These indicate that the combination of DP and PEI is superior to PEI alone as adjuvant,which can provide equal adjuvanticity with lower dose of PEI,thus less toxic.To sum up,the peptide DP,one of the GM1-bps,can enhance antigen-uptake and antigen-presentation when conjugated with the antigen,serving as an adjuvant and molecular carrier to improve the anbody responses.Combination of DP and PEI can further improve it potential for transfection and antigen delivery with lower toxicity.