Impact of RNA modification and IL-12 boosts on mRNA-LNP vaccine-elicited CD8+ T cell responses
Development of effective HIV-1 vaccines requires strategies for inducing both CD8+ T cell and neutralizing antibody responses. Nucleoside-modified mRNA-lipid-nanoparticles (LNP) induce more potent antibody responses than unmodified mRNA-LNP vaccines, while unmodified mRNA is typically employed for CD8+ T cell-inducing vaccines. Here, we compared the abilities of differing ratios of unmodified…
To create effective HIV-1 vaccines, strategies are needed to stimulate both CD8+ T cell and neutralizing antibody responses. Nucleoside-modified mRNA-LNP vaccines produce stronger antibody reactions than unmodified mRNA-LNP vaccines, whereas unmodified mRNA is commonly used for CD8+ T cell-inducing vaccines. Researchers investigated the impact of varying ratios of unmodified versus modified mRNA expressing a SIV conserved-region CD8+ T cell immunogen, when combined with IL-12-encoding mRNA-LNP during boosting, on CD8+ T cell and humoral responses in non-human primates. They also compared these results to ChAdOx1-primed controls.
Serial priming and boosting with unmodified mRNA generated stronger, more CD8-biased T cell responses compared to fully-modified mRNA. These boosted responses persisted over time after IL-12-encoding mRNA boosts. Adding 30% nucleoside-modified mRNA increased antibody levels, indicating that a mixed-composition vaccine may have additional advantages.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
