Posted in Resource, VSV vectors

Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine

Principal Component Analysis plot showing the transcriptomic differences between days 0, 1, 2 and 3 after rVSV∆G-ZEBOV-GP vaccination. Source from F Santoro et al., 2021

rVSV∆G-ZEBOV-GP is a recombinant vaccine based on the Vesicular Stomatitis Virus (VSV), where the original VSV glycoprotein encoding gene was deleted and replaced with the surface glycoprotein (GP) encoding gene from the Ebolavirus Zaire strain (ZEBOV).

The vaccine was shown to be safe, although occasionally associated with transient reactogenicity. However, the host response to the vaccine has not been thoroughly investigated.

In this manuscript by F Santoro et al., 2021, the blood transcriptomic response to high dose vaccination (107 and 5 × 107 pfu) with rVSV∆G- ZEBOV-GP was analysed in 51 volunteers. Whole blood data was taken from day 0, 1, 2, 3, 7, 14, 21 and 28.

Vaccination resulted in greatest host transcriptomic changes at day 1, which lasts till day 3 (see top figure). Notably, the massive transcriptomic changes on days 1-2 corresponds to the timing of occurrence of mild to moderate reactogenicity events (chills, fever, headache, fatigue or myalgia) in 50 out of 51 vaccinees

Viral load differences did not affect host responses to vaccine, except for the MZB1 gene, coding for Marginal Zone B And B1 Cell Specific Protein.

Most blood transcriptomic module correlations with anti-ZEBOV GP IgGs were detected at day 14 post-vaccination. As expected, B cell activation and BCR signaling modules were observed to correlate with vaccine immunogenicity. Other modules that were significantly correlated at day 14 involve pathways such as calcium signalling, cell adhesion and activating transcription factor networks, which are possibly related to signal transduction.

Transcriptomic data are available in the Zenodo database.

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