Blood Test Can Predict How Long Vaccine Immunity Will Last

When children receive their second measles-mumps-rubella vaccine around the time they start kindergarten, they typically gain long-lasting protection against all three viruses. In contrast, the effectiveness of an influenza vaccine, given in October, starts to decrease by the following spring. Researchers have long been puzzled by why some vaccines induce long-lasting antibody production while others offer only short-term immunity. A new study has revealed that the durability of vaccine responses may, in part, be linked to an unexpected type of blood cell called megakaryocytes, which are usually associated with blood clotting.

In the study, scientists from Stanford Medicine (Palo Alto, CA, USA) identified a molecular signature in the blood that forms within days of vaccination and can predict how long the body’s antibody responses will last. In their previous research, the team identified a "universal signature" that could predict the early antibody response to various vaccines, but it did not indicate how long these responses would endure. In their latest work, published in Nature Immunology, the researchers focused on an experimental H5N1 bird flu vaccine, administered with or without an adjuvant— a chemical compound that enhances the immune response to an antigen but does not trigger immunity by itself.

The study tracked 50 healthy volunteers who received two doses of the vaccine, with or without the adjuvant. Blood samples were taken at 12 different time points over the first 100 days after vaccination. The team analyzed the genetic, protein, and antibody composition of these samples, and then used machine learning to analyze the data for patterns. The analysis revealed a specific molecular signature, mostly found in small RNA fragments within platelets, that was strongly correlated with the strength of the antibody response several months after vaccination.

Platelets, which are derived from megakaryocytes in the bone marrow, often carry small RNA pieces from their parent cells when they enter the bloodstream. While tracking megakaryocytes directly is difficult, the RNA in platelets can act as a proxy, reflecting megakaryocyte activity. The Stanford team confirmed this relationship by giving mice both the bird flu vaccine and thrombopoietin, a drug that stimulates the production of activated megakaryocytes in the bone marrow. This treatment led to a sixfold increase in anti-bird flu antibodies two months later. Further experiments showed that activated megakaryocytes produce molecules that promote the survival of plasma cells, which are responsible for antibody production. When these molecules were blocked, fewer plasma cells survived in the presence of megakaryocytes.

To test whether this finding applied to other vaccines, the researchers examined data from 244 individuals who had received seven different vaccines, including those for influenza, yellow fever, malaria, and COVID-19. The same platelet RNA molecules linked to megakaryocyte activation were associated with longer-lasting antibody responses across all these vaccines. The molecular signature not only predicted which vaccines would provide longer-lasting immunity but also indicated which individuals would experience longer-lasting responses. The researchers plan to further investigate why certain vaccines induce higher levels of megakaryocyte activation. These insights could help develop vaccines that more effectively stimulate megakaryocytes, resulting in more durable antibody responses. Additionally, the team aims to create tests to predict how long the immunity from a vaccine will last, potentially speeding up clinical trials and allowing for more personalized vaccination strategies.

“We could develop a simple PCR assay — a vaccine chip — that measures gene expression levels in the blood just a few days after someone is vaccinated,” said Bali Pulendran, PhD, a professor of microbiology and immunology. “This could help us identify who may need a booster and when.”

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