Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice
Document Type
Article
Publication Date
5-1-2024
Abstract
The COVID-19 pandemic has raised the standard regarding the current vaccine development pace, as several messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines have proved their ability to induce strong immunogenicity and protective efficacy. We developed 1-methylpseudouridine-containing mRNA-LNP vaccines, expressing either the more conserved SARS-CoV-2 nucleoprotein (mRNA-N) or spike protein (mRNA-S), both based on the prototypic viral sequences. When combining both mRNA-S and mRNA-N together (mRNA-S+N), the vaccine showed high immunogenicity and broad protection against different SARS-CoV-2 variants, including wildtype, Delta, BA.1, BA.5, and BQ.1. To better understand the mechanisms behind this broad protection obtained by mRNA-S+N, we analyzed innate and adaptive immune parameters following vaccination in mice. Compared to either mRNA-S or mRNA-N alone, mice vaccinated with mRNA-S+N exhibited an increase in the innate immune response, as depicted by the higher cytokine (IL-6 and chemokine (MCP-1) levels. In addition, lymph node immunophenotyping showed the maturation and activation of dendritic cells and natural killer cells, respectively. To understand the adaptive immune response, RNA-Seq analyses of the lung and spleen samples of the vaccinated mice were performed in parallel and revealed a stronger immune gene-expression profile in the lung than that in the spleen. Compared to mRNA-S alone, mRNA-S+N vaccination elicited higher levels of expression for genes involved in multiple immune pathways, including T cells, cytokine signaling, antigen presentation, B cells, and innate immunity. Together, our studies provide immunological insights into the mechanisms of broad protection conferred by dual mRNA vaccination against SARS-CoV-2 variants.
Identifier
85194358084 (Scopus)
Publication Title
Vaccines
External Full Text Location
https://doi.org/10.3390/vaccines12050543
e-ISSN
2076393X
Issue
5
Volume
12
Grant
AI157852
Fund Ref
University of Texas Medical Branch
Recommended Citation
Bonam, Srinivasa Reddy; Hazell, Nicholas C.; Mathew, Mano Joseph; Liang, Yuejin; Zhang, Xuxiang; Wei, Zhi; Alameh, Mohamad Gabriel; Weissman, Drew; and Hu, Haitao, "Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice" (2024). Faculty Publications. 443.
https://digitalcommons.njit.edu/fac_pubs/443
