Spray dried human and chimpanzee adenoviral-vectored vaccines are thermally stable and immunogenic in vivo

被引:25
作者
Afkhami, Sam [1 ,2 ]
LeClair, Daniel A. [3 ]
Haddadi, Siamak [1 ,2 ]
Lai, Rocky [1 ,2 ]
Toniolo, Steven P. [3 ]
Ertl, Hildegund C. [4 ]
Cranston, Emily D. [3 ]
Thompson, Michael R. [3 ]
Xing, Zhou [1 ,2 ]
机构
[1] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON, Canada
[2] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada
[3] McMaster Univ, Dept Chem Engn, Hamilton, ON, Canada
[4] Wistar Inst Anat & Biol, Dept Immunol, 3601 Spruce St, Philadelphia, PA 19104 USA
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
Spray drying; Vaccine; Adenoviral-vectored; Tuberculosis; Thermostability; Animal model; GLASS-TRANSITION TEMPERATURE; MONOCLONAL-ANTIBODY; INFLUENZA VACCINE; IMMUNE-RESPONSES; PARTICLE-SIZE; PROTEIN; TUBERCULOSIS; STABILITY; MUCOSAL; POWDERS;
D O I
10.1016/j.vaccine.2017.04.026
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Cold chain-free vaccine technologies are needed to ensure effective vaccine delivery and coverage, particularly in resource-poor countries. However, the immunogenicity and thermostability of spray dried live viral vector-based vaccines such as recombinant adenoviral-vectored vaccines remain to be investigated. To address this issue, we have spray dried human adenoviral (AdHu5)- and chimpanzee adenoviral (AdCh68)-vectored tuberculosis vaccines in a mannitol and dextran matrix. Spray dried powders containing these two vaccines display the morphologic and chemical properties desired for long-term thermostability and vaccination. Upon reconstitution, they effectively transfected the cells in vitro with relatively small losses in viral infectivity related to the spray drying process. Following in vivo vaccination, AdHu5- and AdCh68-vectored vaccines were as immunogenic as the conventional fresh, cryopreserved liquid vaccine samples. Of importance, even after cold chain-free storage, at ambient temperatures and relatively low humidity for 30 and 90 days, the vaccines retained their in vivo immunogenicity, while the liquid vaccine samples stored under the same conditions lost their immune-activating capability almost entirely. Our results support further development of our spray drying technologies for generating thermally stable adenoviral-vectored and other viral-vectored vaccines. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2916 / 2924
页数:9
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