Mapping the body’s response to mRNA COVID-19 vaccination

Published online 11 November 2022

Insights into how the body responds to two doses of mRNA COVID-19 vaccine could guide future uses.

Lara Reid

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mRNA vaccines have received considerable attention throughout the COVID-19 pandemic, not least because they show potential as a vaccination tool for many other diseases. To ensure that mRNA vaccines realise their full potential, it is important to understand how the body’s immune system responds to them over time.  

An international team, led by Damien Chaussabel, Darawan Rinchai and co-workers at Sidra Medicine in Doha, Qatar, has conducted a comprehensive study based on blood transcriptome profiling of volunteers receiving their first and second doses of mRNA COVID-19 vaccines. 

“No mRNA vaccines had been administered beyond small clinical trials before the approval of the Pfizer and Moderna COVID-19 vaccines, and they have been administered to millions over a short time,” says Rinchai. “We wanted to know precisely what kind of response they elicit, beyond generating antibodies, and how this differs from established vaccine types.”

The team asked 23 healthy volunteers to collect their own blood samples via a simple finger prick test at home. The first blood sample from each volunteer was collected the day before their first vaccination, and then every day for the following nine days. The same was done for the volunteers’ second dose. The vaccine responses were benchmarked against that of patients infected by SARS-CoV-2, with a first cohort contributed by research groups from the Hamad Medical Corporation and Qatar University, and a second from an international group from Italy and Australia. 

“Comprehensive bulk blood transcriptomics profiling allows us to measure and analyse the abundance of tens of thousands of different transcript species from each blood sample,” says Rinchai. 

Their results showed that there was a marked difference in interferon responses following each dose of the vaccine. Interferons are proteins that form a critical part of the body’s immune response – they trigger killer cells to attack pathogens. The first dose triggered a modest interferon and adaptive immune response, which peaked on days two and five. The second dose, by contrast, triggered a sharp interferon and inflammatory response on day one, followed by a spike in plasmablasts on day five. 

“Our study provides a detailed map of how the response to mRNA vaccines unfurls,” says Chaussabel. “These insights could help rationalize the dosing of vaccines and spacing between doses. It may help personalize the process – matching individuals with a specific vaccine that works best for their demographic and health status.”


Rinchai, D. et al. High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines. Science Advances 8, eabp9961 (2022).