Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines

JOURNAL OF CONTROLLED RELEASE

卷:338

Article

Blakney, Anna K.^1,2  McKay, Paul F.²  Hu, Kai²  Samnuan, Karnyart²  Jain, Nikita³  Brown, Andrew³  Thomas, Anitha³  Rogers, Paul²  Polra, Krunal²  Sallah, Hadijatou²  Yeow, Jonathan⁴  Zhu, Yunqing^4,5  Stevens, Molly M.⁴  Geall, Andrew³  Shattock, Robin J.² 

[1] Univ British Columbia, Sch Biomed Engn Vancouver, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada

[2] Imperial Coll London, Dept Infect Dis, London W2 1PG, England

[3] Precis NanoSyst Inc, Vancouver, BC V6P 6T7, Canada

[4] Imperial Coll London, Inst Biomed Engn, Dept Mat, Dept Bioengn, London SW7 2BU, England

[5] Tongji Univ, Sch Mat Sci & Engn, Shanghai 200092, Peoples R China

关键词: Self-amplifying RNA;    Replicon;    Vaccine;    Polyplex;    Lipid nanoparticle;    Protein expression;    Immunogenicity;    SARS-CoV-2;   

DOI  :  10.1016/j.jconrel.2021.08.029

来源: Elsevier

【 摘 要 】

ABSTR A C T Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of admin-istration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines.

【 授权许可】

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