TY - JOUR
T1 - Whole transcriptome profiling identifies CD93 and other plasma cell survival factor genes associated with measles-specific antibody response after vaccination
AU - Haralambieva, Iana H.
AU - Zimmermann, Michael T.
AU - Ovsyannikova, Inna G.
AU - Grill, Diane E.
AU - Oberg, Ann L.
AU - Kennedy, Richard B.
AU - Poland, Gregory A.
N1 - Funding Information:
We thank the Mayo Clinic Vaccine Research Group staff and the study participants. We thank Caroline L. Vitse for her editorial assistance with this manuscript and Nathaniel D. Warner for his programming assistance and contribution to statistical analysis. This work was supported by NIH grants R37AI048793-11, R01AI033144 and was made possible by the Rochester Epidemiology Project (Grant Number R01 AG034676 from the National Institute of Aging). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.
Funding Information:
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.
Publisher Copyright:
© 2016 Haralambieva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0160970
DO - 10.1371/journal.pone.0160970
M3 - Article
C2 - 27529750
AN - SCOPUS:84984830272
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0160970
ER -