佐剂微颗粒疫苗的微针递送在接种冠状病毒疫苗的小鼠中诱导产生高抗体水平。
Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus.
作者信息
Vijayanand Sharon, Patil Smital, Joshi Devyani, Menon Ipshita, Braz Gomes Keegan, Kale Akanksha, Bagwe Priyal, Yacoub Shadi, Uddin Mohammad N, D'Souza Martin J
机构信息
Center for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
出版信息
Vaccines (Basel). 2022 Sep 7;10(9):1491. doi: 10.3390/vaccines10091491.
This 'proof-of-concept' study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with adjuvant MP encapsulating Alhydrogel and AddaVax. We characterized the vaccine MP for size, surface charge, morphology, and encapsulation efficiency. Further, we evaluated the in vitro immunogenicity, cytotoxicity, and antigen-presentation of vaccine/adjuvant MP in murine dendritic cells (DCs). Additionally, we tested the in vivo immunogenicity of the MP vaccine in mice through MN administration. We evaluated the serum IgG, IgA, IgG1, and IgG2a responses using an enzyme-linked immunosorbent assay. The results indicate that the particulate form of the vaccine is more immunogenic than the antigen suspension in vitro. We found the vaccine/adjuvant MP to be non-cytotoxic to DCs. The expression of antigen-presenting molecules, MHC I/II, and their costimulatory molecules, CD80/40, increased with the addition of the adjuvants. Moreover, the results suggest that the MP vaccine is cross presented by the DCs. In vivo, the adjuvanted MP vaccine induced increased antibody levels in mice following vaccination and will further be assessed for its cell-mediated responses.
这项“概念验证”研究旨在测试微粒疫苗递送系统以及使用溶解微针(MN)的经皮疫苗给药策略。为此,我们制备了包裹灭活犬冠状病毒(iCCoV)作为模型抗原的聚乳酸 - 乙醇酸共聚物(PLGA)微粒(MP),以及包裹氢氧化铝凝胶和AddaVax的佐剂MP。我们对疫苗MP的大小、表面电荷、形态和包封效率进行了表征。此外,我们评估了疫苗/佐剂MP在小鼠树突状细胞(DC)中的体外免疫原性、细胞毒性和抗原呈递。另外,我们通过MN给药测试了MP疫苗在小鼠体内的免疫原性。我们使用酶联免疫吸附测定法评估了血清IgG、IgA、IgG1和IgG2a反应。结果表明,疫苗的微粒形式在体外比抗原悬液更具免疫原性。我们发现疫苗/佐剂MP对DC无细胞毒性。随着佐剂的添加,抗原呈递分子MHC I/II及其共刺激分子CD80/40的表达增加。此外,结果表明MP疫苗由DC交叉呈递。在体内,佐剂化的MP疫苗在接种后诱导小鼠体内抗体水平升高,并且将进一步评估其细胞介导的反应。