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Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities

查看全文 作  者:Ye [1]Chen;Qibin [1]Liao;Tianyue [1]Chen;Yuchao [1]Zhang;Weien [2]Yuan;Jianqing [1]Xu;Xiaoyan [1]Zhang 高影响力作者 机构地区:[1]Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences,Fudan University,Shanghai 201508,China;[2]Engineering Research Center of Cell and Therapeutic Antibody,Ministry of Education,and School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200000,China高影响力机构 出  处:《Virologica Sinica》索引2021年第36卷第3期,共8页高影响力期刊 基  金:supported by the National Key R&D Program (2016YFC1303402);the National 13th Five-Year Grand Programon Key Infectious Disease Control (2018ZX10301403, 2017ZX10202102-006);the Intramural Funding from Shanghai Public Health Clinical Center。 摘  要:Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 °C–8 °C. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin(BSA), L-glutamic acid(L-Glu), polyethylene glycol(PEG), and dextran(DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine(rTTV-OVA) and adenovirus vaccine(Ad5-ENV). We compared a panel of five different formulations(PEG: DEX: BSA: L-GLU = 50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3),50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 °C and25 °C and that r TTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature. 关 键 词:Adenovirus vaccine Poxvirus vaccine Freeze-drying formulation Stability IMMUNOGENICITY
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