Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines

基于短碳纳米管的mRNA递送系统在HIV-1疫苗中的应用

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作者:Yang Xu ,Tammy Ferguson ,Kazuya Masuda ,Mohammad Adnan Siddiqui ,Kelsi Poole Smith ,Olivia Vest ,Brad Brooks ,Ziyou Zhou ,Judy Obliosca ,Xiang-Peng Kong ,Xunqing Jiang ,Masahiro Yamashita ,Tsuji Moriya ,Christopher Tison

Abstract

Developing a safe and effective preventive for HIV-1 remains the hope for controlling the global AIDS epidemic. Recently, mRNA vaccines have emerged as a promising alternative to conventional vaccine approaches, primarily due to their rapid development and potential for low-cost manufacture. Despite the advantages of mRNA vaccines, challenges remain, especially due to the adverse effects of the delivery vehicle and low delivery efficiency. As a result, Luna Labs is developing a short carbon nanotube-based delivery platform (NanoVac) that can co-deliver mRNA and HIV-1 glycoproteins to the immune system efficiently with negligible toxicity. Surface chemistries of NanoVac were optimized to guide antigen/mRNA loading density and presentation. Multiple formulations were engineered for compatibility with both intramuscular and intranasal administration. NanoVac candidates demonstrated immunogenicity in rabbits and generated human-derived humoral and cellular responses in humanized mice (HIS). Briefly, 33% of the HIV-1-infected HIS mice vaccinated with NanoVac-mRNA was cleared of virus infection by 8-weeks post-infection. Finally, NanoVac stabilized the loaded mRNA against degradation under refrigeration for at least three months, reducing the cold chain burden for vaccine deployment.

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