Blood Test Predicts Vaccine Immunogenicity

A blood test early after vaccination can predict whether vaccines based on living, modified viruses have had the desired effect within seven days of vaccination.

A new study on systems analysis of immune responses induced by a highly promising vaccine against Ebola, as a couple of possible vaccines have been proposed, and this can inform and accelerate rational development of other new vaccines based on living viruses.

One of the vaccines, which is based on a recombinant vesicular stomatitis virus expressing the glycoprotein of the Zaire strain of the Ebola virus (VSV-ZEBOV), was recently shown to be extremely effective with 100% efficacy against the lethal Ebola virus disease in studies carried out in Guinea and Sierra Leone.

A large team of international scientists collaborating with those at the Geneva University Hospitals and Faculty of Medicine examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day one. The study includes 190 healthy individuals from Africa and Europe.

By longitudinal analysis blood samples retrieved from persons who have received the Ebola vaccine, the team could show that a group of cytokines measured in plasma within seven days of the vaccine injection correlates with antibody responses developed six months later. The cytokine signature was also shown to correlate with vaccine reactogenicity observed in some volunteers. A signature explaining 68% of cytokine/chemokine vaccine-response variability was identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees that subsequently developed arthritis had lower day one scores than other HD vaccinees. This signature, which reveals monocytes’ critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines.

Ali M. Harandi, PhD, a co-author of the study said, “The results can also provide information to discover biomarkers for other vaccines based on living vectors. There are ongoing studies which focus on the discovery of molecular biomarkers of the VSV-ZEBOV vaccine in healthy individuals using omics-based technologies in combination with a systems biology approach.” The study was published on April 12, 2017, in the journal Science Translational Medicine.