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基于短碳纳米管的 HIV-1 疫苗 mRNA 递呈。

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

机构信息

Luna Labs USA, 706 Forest St. Suite A, Charlottesville, VA 22903, USA.

Aaron Diamond AIDS Research Center, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.

出版信息

Biomolecules. 2023 Jul 7;13(7):1088. doi: 10.3390/biom13071088.

DOI:10.3390/biom13071088
PMID:37509124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10377108/
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.

摘要

开发安全有效的 HIV-1 预防性疫苗仍然是控制全球艾滋病流行的希望。最近，mRNA 疫苗作为传统疫苗方法的一种有前途的替代方案出现，主要是因为它们可以快速开发并且具有低成本制造的潜力。尽管 mRNA 疫苗具有优势，但仍存在挑战，特别是由于输送载体的不良反应和低输送效率。为此，Luna Labs 正在开发一种基于短碳纤维纳米管的输送平台（NanoVac），该平台可以有效地将 mRNA 和 HIV-1 糖蛋白共输送到免疫系统，几乎没有毒性。NanoVac 的表面化学性质经过优化，可指导抗原/mRNA 的加载密度和呈现。针对多种配方进行了工程设计，以适应肌内和鼻内给药。NanoVac 候选物在兔子中表现出免疫原性，并在人源化小鼠（HIS）中产生了人类来源的体液和细胞反应。简而言之，33%的感染了 HIV-1 的 HIS 小鼠在接种 NanoVac-mRNA 后 8 周内清除了病毒感染。最后，NanoVac 使负载的 mRNA 在冷藏下稳定至少三个月，减少了疫苗部署的冷链负担。

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