Pulmonary
Partner With Us
Advertisement
From the Journals

Platelet Signature Predicts Antibody Longevity Across Vaccines

Study identifies platelet activity as a predictor of antibody durability in vaccines.

Conexiant

Stanford University researchers identified a blood transcriptional signature related to platelets and cell adhesion that predicts antibody response durability across multiple vaccines, according to a study published in Nature Immunology.

The randomized clinical trial enrolled 50 healthy adults aged 21 to 45 years who received 2 doses of the H5N1 avian influenza vaccine. Participants were randomized 2:1 to receive the vaccine with (n = 34) or without (n = 16) the AS03 adjuvant. By day 42, the AS03-adjuvanted group exhibited significantly higher geometric mean hemagglutination inhibition (HAI) titers versus controls. Microneutralization (MN) titers also differed: 523.3 versus 22.8. Seroconversion rates at day 42 were 70% (HAI) and 97% (MN) in the adjuvanted group, compared to 0% (HAI) and 25% (MN) in the unadjuvanted group.

Using machine learning, researchers found that a platelet-related signature accurately predicted antibody durability across six vaccines. The area under the curve (AUC) values for prediction were:

  • 0.78 in the training set (H5N1+AS03)

  • 0.93 in the validation set (seasonal influenza)

  • 0.72 for the Pfizer-BioNTech COVID-19 vaccine

  • 0.86 for the meningococcal vaccine (MPSV4)

  • 0.70 for RTS,S malaria vaccine

  • 0.75 for pneumococcal conjugate vaccine (PCV-13)

In mouse models, thrombopoietin (TPO) administration was associated with an 18-fold increase in anti-Spike antibody titers at 21 days post-vaccination and a sixfold increase at 2 months.

Cellular analyses revealed TPO-activated megakaryocytes promoted plasma cell survival through integrin β1/β2-mediated interactions and the APRIL and MIF-CD74 axes. Single-cell RNA sequencing (CITE-seq) identified platelets as major contributors to the transcriptional signature of antibody durability.

The study employed robust molecular analyses, including RNA sequencing and flow cytometry, with blood samples collected at multiple time points (days 0, 1, 3, 7, 14, 21, 22, 24, 28, 35, 42, and 100). Researchers validated their findings across non-human primate models, further supporting the conserved mechanism linking platelet activity to long-term immunity.

Conflict of interest disclosures can be found in the study.