Microneedles Fabricated with Multifunctional Liposomes for Vaginal Vaccine Delivery
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- 英文论文题名：Microneedles Fabricated with Multifunctional Liposomes for Vaginal Vaccine Delivery
- 论文作者：Wang Ting ; Zhen Yuanyuan ; Wang Xueting ; Li Ning ; Wang Ning
- 英文论文作者：Wang Ting ; Zhen Yuanyuan ; Wang Xueting ; Li Ning ; Wang Ning ; Anhui Medical University School of Pharmacy ; Hefei University of Technology School of Biological and Medical Engineering
- 年：2016
- 作者机构：Anhui Medical University School of Pharmacy;Hefei University of Technology School of Biological and Medical Engineering;
- 英文论文关键词：microneedle ; vaginal vaccination ; lysosome escape ; cross presentation ; mucosal immunity
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会壁报交流集
- 英文会议录名称：Proceedings of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R392
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1297k
- 原文格式：D
- 会议级别：全国
摘要
Background:Sexually transmitted infections(STI) caused by pathogens,such as HIV and HSV,are hazardous to human health and even threaten their lives.Though vaccination is efficient in preventing the infectious diseases,there is still a severe lack of effective products,especially the subunit vaccines,against STI.Purposes:It is aimed to develop an effective vaccine adjuvant-delivery system(VADS) that can be used to engender mucosal vaccines to STI.Methods:Two types of liposomes,the mannosylated lipid A-liposomes(MLLs) and the stealth lipid A-liposomes(SLLs),both loaded with a model antigen ovalbumin and ammonium bicarbonate(NH4HCO3),were prepared and fabricated together into microneedles to form the pro SLL/MLL-constituted microneedle array(pro SMMA),which were tested as a VADS on mice through administration by vaginal mucosa patching.Results:The anhydrous pro SMMAs were stable and,upon rehydration,recovering the initial MLLs and SLLs without change in size and structure.Mice vaccinated by vaginal mucosa patching with pro SMMAs established robust cellular and humoral immunity to the loaded antigens at both systemic and mucosal levels,especially,in the reproductive and intestinal ducts.Further exploration demonstrated that,while the MLLs reconstituted in situ from the inoculated pro SMMAs were mostly taken up by local mucosal dendritic cells,the simultaneously recovered SLLs trafficked to the draining sentinel lymph nodes and were picked up therein mainly by medulla macrophages.Moreover,the antigens delivered by either liposomes were processed by APCs through cross-presentation pathway thanks to lysosomal escape,which occurred upon acidifying the vesicle-delivered NH4HCO3 to release CO2 gas and NH4+/NH3;while the gas caused lyso-some rupture by swelling,NH4+/NH3 induced production of ROS to promote MHC-I presentation,leading to efficient production of cytotoxic T lymphocytes.Conclusions:The pro SMMAs may be an effective VADS fulfilling the mucosal/lymph node dual delivery function to elicit robust immunity against STI.
Background:Sexually transmitted infections(STI) caused by pathogens,such as HIV and HSV,are hazardous to human health and even threaten their lives.Though vaccination is efficient in preventing the infectious diseases,there is still a severe lack of effective products,especially the subunit vaccines,against STI.Purposes:It is aimed to develop an effective vaccine adjuvant-delivery system(VADS) that can be used to engender mucosal vaccines to STI.Methods:Two types of liposomes,the mannosylated lipid A-liposomes(MLLs) and the stealth lipid A-liposomes(SLLs),both loaded with a model antigen ovalbumin and ammonium bicarbonate(NH4HCO3),were prepared and fabricated together into microneedles to form the pro SLL/MLL-constituted microneedle array(pro SMMA),which were tested as a VADS on mice through administration by vaginal mucosa patching.Results:The anhydrous pro SMMAs were stable and,upon rehydration,recovering the initial MLLs and SLLs without change in size and structure.Mice vaccinated by vaginal mucosa patching with pro SMMAs established robust cellular and humoral immunity to the loaded antigens at both systemic and mucosal levels,especially,in the reproductive and intestinal ducts.Further exploration demonstrated that,while the MLLs reconstituted in situ from the inoculated pro SMMAs were mostly taken up by local mucosal dendritic cells,the simultaneously recovered SLLs trafficked to the draining sentinel lymph nodes and were picked up therein mainly by medulla macrophages.Moreover,the antigens delivered by either liposomes were processed by APCs through cross-presentation pathway thanks to lysosomal escape,which occurred upon acidifying the vesicle-delivered NH4HCO3 to release CO2 gas and NH4+/NH3;while the gas caused lyso-some rupture by swelling,NH4+/NH3 induced production of ROS to promote MHC-I presentation,leading to efficient production of cytotoxic T lymphocytes.Conclusions:The pro SMMAs may be an effective VADS fulfilling the mucosal/lymph node dual delivery function to elicit robust immunity against STI.
Background:Sexually transmitted infections(STI) caused by pathogens,such as HIV and HSV,are hazardous to human health and even threaten their lives.Though vaccination is efficient in preventing the infectious diseases,there is still a severe lack of effective products,especially the subunit vaccines,against STI.Purposes:It is aimed to develop an effective vaccine adjuvant-delivery system(VADS) that can be used to engender mucosal vaccines to STI.Methods:Two types of liposomes,the mannosylated lipid A-liposomes(MLLs) and the stealth lipid A-liposomes(SLLs),both loaded with a model antigen ovalbumin and ammonium bicarbonate(NH4HCO3),were prepared and fabricated together into microneedles to form the pro SLL/MLL-constituted microneedle array(pro SMMA),which were tested as a VADS on mice through administration by vaginal mucosa patching.Results:The anhydrous pro SMMAs were stable and,upon rehydration,recovering the initial MLLs and SLLs without change in size and structure.Mice vaccinated by vaginal mucosa patching with pro SMMAs established robust cellular and humoral immunity to the loaded antigens at both systemic and mucosal levels,especially,in the reproductive and intestinal ducts.Further exploration demonstrated that,while the MLLs reconstituted in situ from the inoculated pro SMMAs were mostly taken up by local mucosal dendritic cells,the simultaneously recovered SLLs trafficked to the draining sentinel lymph nodes and were picked up therein mainly by medulla macrophages.Moreover,the antigens delivered by either liposomes were processed by APCs through cross-presentation pathway thanks to lysosomal escape,which occurred upon acidifying the vesicle-delivered NH4HCO3 to release CO2 gas and NH4+/NH3;while the gas caused lyso-some rupture by swelling,NH4+/NH3 induced production of ROS to promote MHC-I presentation,leading to efficient production of cytotoxic T lymphocytes.Conclusions:The pro SMMAs may be an effective VADS fulfilling the mucosal/lymph node dual delivery function to elicit robust immunity against STI.
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