In practice, when children receive their 2nd booster vaccination against measles, mumps and rubella (MMR), around the time they enter kindergarten, they benefit from protection against the 3 viruses throughout their entire life. life or most of their lives. On the other hand, the effectiveness of a flu vaccine administered in October decreases on average in the following spring, and with differences depending on the individual.
Scientists have long wondered why some vaccines can prompt the body to produce antibodies for decades, while others last only a few months. This news reveals that variation in vaccine durability can, in part, be attributed to a surprising type of blood cell called megakaryocytes, generally involved in blood clotting.
Lead author Dr. Bali Pulendran, professor of microbiology and immunology at Stanford, adds: “The question of why some vaccines induce lasting immunity while others do not, is one of the great mysteries of immunology. Our work identifies a molecular signature in the blood, induced a few days after vaccination, which predicts the durability of the vaccine response and also provides new understanding of the fundamental mechanisms underlying vaccine durability.”
A molecular signature in the blood that predicts the durability of the vaccine response
Previous research by the same team had already identified a “universal signature” that could predict an early antibody response to many vaccines.
The study first focused on an experimental vaccine against H5N1 avian flu administered with an adjuvant – a cocktail that strengthens the immune response to an antigen but which, on its own, does not induce an immune response. The study followed 50 healthy participants who received either 2 doses of avian influenza vaccine with the adjuvant or 2 doses without the adjuvant. Blood samples were taken from the participants on a dozen occasions during the first 100 days following vaccination. The team also developed a machine learning (AI) program to identify “immunity” patterns. The analysis reveals:
-- a molecular signature in the blood in the days following vaccination, associated with the strength of the antibody response months after vaccination;
- the signature is expressed primarily in tiny pieces of RNA in platelets – small cells that form clots in the blood;
- However, platelets are derived from megakaryocytes, cells present in the bone marrow. When they break away from megakaryocytes and enter the bloodstream, platelets often carry small pieces of megakaryocyte RNA with them;
- thus, platelets are an indicator of what is happening with megakaryocytes in the bone marrow and of vaccination-induced immunity.
The proof of this molecular signature concept carried by megakaryocytes is provided in model mice, vaccinated with the avian flu vaccine and thrombopoietin, a drug which increases the number of activated megakaryocytes in the bone marrow:
- activated megakaryocytes produce key molecules that increase the survival of bone marrow cells responsible for making antibodies, or plasma cells;
In conclusion, megakaryocytes provide a nourishing environment conducive to the survival of plasma cells in the bone marrow.
This result also applies to other types of vaccines: analysis of vaccine response data (antibodies) from 244 participants, having received 7 different vaccines, including the vaccine against seasonal flu, yellow fever, malaria and COVID-19, reveals that the same platelet RNA molecules – signs of megakaryocyte activation – are associated with more durable antibody production for the different vaccines.
The molecular signature could thus predict which vaccines last longer and identify recipients developing a more durable response.
Towards personalized vaccination? The objective today is to develop tests to determine, using the new molecular signature, the probable lifespan of a vaccine. This would not only accelerate vaccine clinical trials but also ultimately develop personalized vaccination plans.
