Nano Today . A Highly Efficient Needle-Free-Injection Delivery System for mRNA-LNP Vaccination against SARS-CoV-2

[tetano]

Nano Today


. 2022 Dec 21;48:101730.
doi: 10.1016/j.nantod.2022.101730. Online ahead of print.
A Highly Efficient Needle-Free-Injection Delivery System for mRNA-LNP Vaccination against SARS-CoV-2


Shanhong Mao ^{1 2} , Shiyou Li ³ , Yuxin Zhang ⁴ , Luoxin Long ¹ , Junfeng Peng ³ , Yuanyan Cao ¹ , Jessica Z Mao ⁵ , Xin Qi ⁴ , Qi Xin ³ , Guoliang San ⁴ , Jing Ding ⁴ , Jun Jiang ³ , Xuejiao Bai ³ , Qianting Wang ³ , Pengfei Xu ³ , Huan Xia ³ , Lijun Lu ³ , Liangzhi Xie ⁶ , Desheng Kong ⁶ , Shuangli Zhu ⁷ , Wenbo Xu ⁷



Affiliations

• PMID: 36570700
• PMCID: PMC9767897
• DOI: 10.1016/j.nantod.2022.101730

Abstract

Despite the various vaccines that have been developed to combat the coronavirus disease 2019 (COVID-19) pandemic, the persistent and unpredictable mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require innovative and unremitting solutions to cope with the resultant immune evasion and establish a sustainable immune barrier. Here we introduce a vaccine-delivery system with a combination of a needle-free injection (NFI) device and a SARS-CoV-2-Spike-specific mRNA-Lipid Nanoparticle (LNP) vaccine. The benefits are duller pain and a significant increase of immunogenicity compared to the canonical needle injection (NI). From physicochemical and bioactivity analyses, the structure of the mRNA-LNP maintains stability upon NFI, contradictory to the belief that LNPs are inclined towards destruction under the high-pressure conditions of NFI. Moreover, mRNA-LNP vaccine delivered by NFI induces significantly more binding and neutralizing antibodies against SARS-CoV-2 variants than the same vaccine delivered by NI. Heterogeneous vaccination of BA.5-LNP vaccine with NFI enhanced the generation of neutralizing antibodies against Omicron BA.5 variants in rabbits previously vaccinated with non-BA.5-specific mRNA-LNP or other COVID-19 vaccines. NFI parameters can be adjusted to deliver mRNA-LNP subcutaneously or intramuscularly. Taken together, our results suggest that NFI-based mRNA-LNP vaccination is an effective substitute for the traditional NI-based mRNA-LNP vaccination.

Keywords: Lipid Nanoparticle (LNP); Needle injection (NI); Needle-free injection (NFI); SARS-CoV-2; mRNA vaccine.