Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.
Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.
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DOI：
10.3390/biom13071088
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发表时间：
2023-07-07
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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开发安全有效的 HIV-1 预防措施仍然是控制全球艾滋病流行的希望。最近，mRNA 疫苗已成为传统疫苗方法的有前途的替代品，这主要是由于其快速发展和低成本制造的潜力。尽管 mRNA 疫苗具有优势，但挑战仍然存在，特别是由于递送载体的不利影响和递送效率低。因此，Luna Labs 正在开发一种基于碳纳米管的短递送平台 (NanoVac)，该平台可以有效地将 mRNA 和 HIV-1 糖蛋白共同递送至免疫系统，且毒性可忽略不计。 NanoVac 的表面化学经过优化，可指导抗原/mRNA 的装载密度和呈递。设计了多种制剂以兼容肌内和鼻内给药。 NanoVac 候选物在兔子中表现出免疫原性，并在人源化小鼠 (HIS) 中产生人源性体液和细胞反应。简而言之，接种 NanoVac-mRNA 疫苗的 HIV-1 感染 HIS 小鼠中有 33% 在感染后 8 周清除了病毒感染。最后，NanoVac 在冷藏条件下稳定加载的 mRNA 至少三个月，防止降解，从而减轻了疫苗部署的冷链负担。
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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影响因子：
16.6
作者：
Weiss S;Itri V;Pan R;Jiang X;Luo CC;Morris L;Malherbe DC;Barnette P;Alexander J;Kong XP;Haigwood NL;Hessell AJ;Duerr R;Zolla-Pazner S
通讯作者：
Zolla-Pazner S
DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
5.5
作者：
Zou W;Xing J;Zou S;Jiang M;Chen X;Chen Q;Liu D;Zhang X;Fu X
通讯作者：
Fu X
影响因子：
3.2
作者：
Baxter MFA;Merino-Guzman R;Latorre JD;Mahaffey BD;Yang Y;Teague KD;Graham LE;Wolfenden AD;Hernandez-Velasco X;Bielke LR;Hargis BM;Tellez G
通讯作者：
Tellez G
影响因子：
8.8
作者：
Hessell, Ann J.;Powell, Rebecca;Zolla-Pazner, Susan
通讯作者：
Zolla-Pazner, Susan