Abstract
BackgroundThere 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.MethodsWe 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.ResultsWe 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.ConclusionWe 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.
Highlights
Despite the widespread use of measles vaccines and the dramatic decrease in the occurrence of measles in the U.S, annual outbreaks involving hundreds of cases continue to occur.[1]
We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value0.0002, q-value0.092), including the top gene CD93 (p
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
Summary
Despite the widespread use of measles vaccines (especially the two-dose immunization schedule introduced in 1989) and the dramatic decrease in the occurrence of measles in the U.S, annual outbreaks involving hundreds of cases continue to occur.[1]. There are insufficient data on the immunologic, genetic and genomic basis of inter-individual immune response variations after measles vaccination to help uncover the molecular mechanisms underlying vaccine failure. Comprehensive omics-level information on measles vaccine immune responses and waning immunity has not been previously generated. To fill these knowledge gaps, we developed a new vaccinomics paradigm that utilizes unbiased, highdimensional omics data and advanced statistical/bioinformatics approaches for deep immune profiling of viral vaccine responses.[5,6,7] The ultimate goal is to apply these approaches to identify signatures (containing both individual variables and their interactions) that can discriminate among measles vaccine immune phenotypes, serve as biomarkers of protective immunity, and inform the development of novel vaccine candidates. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
