Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines

Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines

npj Vaccines

10.1038/s41541-024-00835-x

http://dx.doi.org/10.1038/s41541-024-00835-x

Ki Hyun Bae, Bhuvaneshwari Shunmuganathan, Li Zhang, Andrew Lim, Rashi Gupta, Yanming Wang, Boon Lin Chua, Yang Wang, Yue Gu, Xinlei Qian, Isabelle Siang Ling Tan, Kiren Purushotorman, Paul A. MacAry, Kevin P. White, Yi Yan Yang

Immunology, Infectious Diseases, Pharmacology, Pharmacology (medical)

23 February 2024

Bae, K. H., Shunmuganathan, B., Zhang, L., Lim, A., Gupta, R., Wang, Y., Chua, B. L., Wang, Y., Gu, Y., Qian, X., Tan, I. S. L., Purushotorman, K., MacAry, P. A., White, K. P., & Yang, Y. Y. (2024). Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines. Npj Vaccines, 9(1). https://doi.org/10.1038/s41541-024-00835-x

AbstractThe advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), and high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: Bioprocessing Technology Institute (BTI)
Grant Reference no. : NA

This research is supported by core funding from: Genome Institute of Singapore (GIS)
Grant Reference no. : NA

This research / project is supported by the A*STAR - Use Inspired Basic Research (UIBR) grant
Grant Reference no. : NA

https://oar.a-star.edu.sg/communities-collections/articles/19697

2059-0105

Bioprocessing Technology Institute

https://doi.org/10.1038/s41541-024-00835-x