角鲨烯
TLR7型
TLR4型
免疫系统
佐剂
兴奋剂
受体
抗原
Toll样受体
抗体
生物
化学
免疫学
生物化学
先天免疫系统
作者
Kristopher K. Short,Stephanie K. Lathrop,Clara J. Davison,Haley A. Partlow,Johnathan A. Kaiser,Rebekah Tee,Elizabeth B. Lorentz,Jay T. Evans,David J. Burkhart
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2022-07-12
卷期号:14 (7): 1455-1455
被引量:5
标识
DOI:10.3390/pharmaceutics14071455
摘要
A diversity of vaccines is necessary to reduce the mortality and morbidity of SARS-CoV-2. Vaccines must be efficacious, easy to manufacture, and stable within the existing cold chain to improve their availability around the world. Recombinant protein subunit vaccines adjuvanted with squalene-based emulsions such as AS03™ and MF59™ have a long and robust history of safe, efficacious use with straightforward production and distribution. Here, subunit vaccines were made with squalene-based emulsions containing novel, synthetic toll-like receptor (TLR) agonists, INI-2002 (TLR4 agonist) and INI-4001 (TLR7/8 agonist), using the recombinant receptor-binding domain (RBD) of SARS-CoV-2 S protein as an antigen. The addition of the TLR4 and TLR7/8 agonists, alone or in combination, maintained the formulation characteristics of squalene-based emulsions, including a sterile filterable droplet size (<220 nm), high homogeneity, and colloidal stability after months of storage at 4, 25, and 40 °C. Furthermore, the addition of the TLR agonists skewed the immune response from Th2 towards Th1 in immunized C57BL/6 mice, resulting in an increased production of IgG2c antibodies and a lower antigen-specific production of IL-5 with a higher production of IFNγ by lymphocytes. As such, incorporating TLR4 and TLR7/8 agonists into emulsions leveraged the desirable formulation and stability characteristics of emulsions and can induce Th1-type humoral and cell-mediated immune responses to combat the continued threat of SARS-CoV-2.
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