Polymeric cGAMP microparticles affect the immunogenicity of a broadly active influenza mRNA lipid nanoparticle vaccine

被引:2
|
作者
Hendy, Dylan A. [1 ]
Ma, Yutian [1 ]
Dixon, Timothy A. [1 ]
Murphy, Connor T. [1 ]
Pena, Erik S. [2 ,3 ]
Carlock, Michael A. [4 ]
Ross, Ted M. [4 ,5 ,6 ]
Bachelder, Eric M. [1 ]
Ainslie, Kristy M. [1 ,2 ,3 ,7 ]
Fenton, Owen S. [1 ]
机构
[1] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27695 USA
[2] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Chapel Hill, NC USA
[3] North Carolina State Univ, Raleigh, NC USA
[4] Port St Cleveland Clin Florida, Florida Res & Innovat Ctr, Port St Lucie, FL USA
[5] Univ Georgia, Ctr Vaccines & Immunol, Athens, GA USA
[6] Univ Georgia, Dept Infect Dis, Athens, GA USA
[7] Univ N Carolina, UNC Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC USA
基金
美国国家卫生研究院;
关键词
Acetalated dextran; COBRA; STING; Infectious disease; DEXTRAN; DEGRADATION; ANTIBODIES; IMMUNITY; ADJUVANT;
D O I
10.1016/j.jconrel.2024.06.007
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Influenza outbreaks are a major burden worldwide annually. While seasonal vaccines do provide protection against infection, they are limited in that they need to be updated every year to account for the constantly mutating virus. Recently, lipid nanoparticles (LNPs) encapsulating mRNA have seen major success as a vaccine platform for SARS-CoV-2. Herein, we applied LNPs to deliver an mRNA encoding a computationally optimized broadly active (COBRA) influenza immunogen. These COBRA mRNA LNPs induced a broadly active neutralizing antibody response and protection after lethal influenza challenge. To further increase the immunogenicity of the COBRA mRNA LNPs, we combined them with acetalated dextran microparticles encapsulating a STING agonist. Contrary to recent findings, the STING agonist decreased the immunogenicity of the COBRA mRNA LNPs which was likely due to a decrease in mRNA translation as shown in vitro. Overall, this work aids in future selection of adjuvants to use with mRNA LNP vaccines.
引用
收藏
页码:168 / 175
页数:8
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