How do we know if a vaccine protects for life, like the one against measles, or only for a few months like those for the flu or Covid-19? The answer could be found in cells in our bone marrow, according to new work published in the journal Nature ImmunologyA simple blood test would allow us to detect a predictive marker of this duration of action.
“ One of the main goals of vaccinology is to predict, before administration to humans or within a few days after vaccination, the length of time a vaccine will remain protective.", explains Bali Pulendran, professor of microbiology and immunology at Stanford University (United States). Until now, the only way to determine this duration of protection was to "wait and see "months or even years after vaccination, and to assess whether the immune protection was still active," he continues.
A piece of RNA attaches to blood platelets
The mystery is finally being solved thanks to the team's work using systems biology, i.e. the complete analysis of the expression (activation) of the entire genome, as well as a series of proteins and metabolites, from blood samples. The researchers identify in particular an element associated with blood platelets - these cells allowing blood clotting - as predictive of the intensity of the immune response after vaccination.
These observations come from blood tests of 50 healthy volunteers who received two doses of a vaccine against H5N1 bird flu – the subject of their research at that time – with or without adjuvant, a substance present in many vaccines and which increases their effectiveness.
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Subjects who received a vaccine with adjuvant benefit by definition from a more intense immune protection. It is in their blood that researchers identify small pieces of genetic material attached to the platelets, more precisely RNA, specifies Bali Pulendran. This RNA actually comes from megakaryocytes, large cells of the bone marrow that produce platelets. Platelets carry small fragments of RNA from their parent cells", summarizes Bali Pulendran. While it is difficult to observe the activity of megakaryocytes in the bone marrow, these fragments serve as an indicator.
A factor that would promote the survival of antibody-producing cells
But what is the relationship between the duration of the immune response after vaccination and the cells producing blood platelets? Professor Pulendran admits to being surprised. Platelets and megakaryocytes are not the first cell types that come to mind when considering the durability of immune responses.. » This is indeed the case. When scientists administered the vaccine to mice combined with thrombopoietin, a drug that activates megakaryocytes, the level of anti-H5N1 antibodies increased sixfold after two months!
“ Our hypothesis is that megakaryocytes provide plasma cells (cells that produce antibodies, editor's note) a nourishing and survival-friendly environment in the bone marrow" explains Bali Pulendran. Also located in the bone marrow, plasma cells survive better in the presence of molecules produced by megakaryocytes, according to previous studies.
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Towards a blood test predicting the duration of effectiveness of a vaccine
“ We discovered a unique molecular signature of the first seven days after vaccination that could predict the longevity of an individual's antibody response months later", summarizes Bali Pulendran. This signature also appears to be valid for other vaccines against influenza, malaria, Covid-19 and pneumococcal and meningococcal diseases (bacteria), according to analyses using AI-driven machine learning on six different vaccines, evaluated in seven separate trials involving 244 participants. " This suggests that a fundamental and conserved mechanism may underlie the durability of vaccine-induced immune responses.", points out Bali Pulendran.
He hopes the findings will pave the way for a simple blood test that could be used to predict the durability of the response, either before or within days of vaccination. To develop the blood test, the researchers are already planning to test the signature in samples collected in studies of other vaccines given to populations around the world.
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