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. 2016 Aug 16;11(8):e0160970.
doi: 10.1371/journal.pone.0160970. eCollection 2016.

Whole Transcriptome Profiling Identifies CD93 and Other Plasma Cell Survival Factor Genes Associated with Measles-Specific Antibody Response after Vaccination

Iana H Haralambieva  1 , Michael T Zimmermann  2 , Inna G Ovsyannikova  1 , Diane E Grill  2 , Ann L Oberg  2 , Richard B Kennedy  1 , Gregory A Poland  1
Affiliations

Whole Transcriptome Profiling Identifies CD93 and Other Plasma Cell Survival Factor Genes Associated with Measles-Specific Antibody Response after Vaccination

Iana H Haralambieva et al. PLoS One. .

Abstract

Background: There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals.

Methods: We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response.

Results: We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value≤0.0002, q-value≤0.092), including the top gene CD93 (p<1.0E-13, q<1.0E-09), encoding a receptor required for antigen-driven B-cell differentiation, maintenance of immunoglobulin production and preservation of plasma cells in the bone marrow. Network biology modeling highlighted plasma cell survival (CD93, IL6, CXCL12), chemokine/cytokine activity and cell-cell communication/adhesion/migration as biological processes associated with the observed differential response in the two responder groups.

Conclusion: We identified genes and pathways that explain in part, and are associated with, neutralizing antibody titers after measles vaccination. This new knowledge could assist in the identification of biomarkers and predictive signatures of protective immunity that may be useful in the design of new vaccine candidates and in clinical studies.

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Conflict of interest statement

Competing Interests: Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Dynavax, Novartis Vaccines and Therapeutics, Emergent Biosolutions, Adjuvance, Microdermis, Seqirus, NewLink, Protein Sciences, GSK Vaccines, and Sanofi Pasteur. Dr. Poland holds two patents related to vaccinia and measles peptide research. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Legend.
Network biology of gene expression in measles vaccine high and low antibody responders.Simultaneous visualization of overall stimulation response (gene expression in response to viral stimulation in all subjects) and differential responses (in high vs. low antibody responders) within the context of a high-confidence biologic network. Each gene is represented as two circles, the outer colored by the virus-induced fold change in all subjects (FC, presented as log2 Stim FC) and the inner by the statistical interaction between high and low responders (i.e., difference in stimulated FC between the high and low antibody responder groups, presented as log2 FC between high and low responders).
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