A highly efficient needle-free-injection delivery system for mRNA-LNP vaccination against SARS-CoV-2

Area of Science:

• Immunology
• Vaccinology
• Nanotechnology

Background:

• Persistent SARS-CoV-2 mutations necessitate advanced vaccine strategies to overcome immune evasion.
• Current COVID-19 vaccines face challenges due to viral evolution and the need for sustainable immune barriers.

Purpose of the Study:

• To evaluate a novel vaccine delivery system combining needle-free injection (NFI) with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-Spike-specific messenger RNA-Lipid Nanoparticle (mRNA-LNP) vaccine.
• To compare the immunogenicity and efficacy of NFI-delivered mRNA-LNP vaccines against traditional needle injection (NI).

Main Methods:

• Physicochemical and bioactivity analyses of mRNA-LNP stability under NFI conditions.
• Comparative immunogenicity studies in rabbits using NFI versus NI delivery of mRNA-LNP vaccines against SARS-CoV-2 variants.
• Assessment of binding and neutralizing antibody responses, including heterogeneous vaccination strategies.

Main Results:

• mRNA-LNP vaccine structure remained stable when delivered via NFI, challenging prior assumptions about LNP fragility.
• NFI delivery of mRNA-LNP vaccines elicited significantly higher binding and neutralizing antibodies against SARS-CoV-2 variants compared to NI.
• Heterogeneous vaccination using an Omicron BA.5-LNP vaccine via NFI boosted neutralizing antibodies against the BA.5 variant in previously vaccinated rabbits.

Conclusions:

• NFI is a viable and effective delivery method for mRNA-LNP vaccines, demonstrating superior immunogenicity and stability.
• NFI-based mRNA-LNP vaccination presents a promising alternative to traditional needle-based vaccination for combating COVID-19 and its variants.
• Adjustable NFI parameters allow for both subcutaneous and intramuscular delivery, enhancing vaccination flexibility.