Systems Immunology, Antibody repertoire analysis, Immunoprofiling in health and disease

In the Wine research group we aim to profile the molecular composition of antibodies following vaccine or disease. To accomplish this aim, we use our recently developed technology to elucidate the identities of antibodies directly from human blood or secretions.
Our technology is based on a two-arm foundation:
a) Proteomic analysis of serum/secretion antibodies utilizing shotgun high-resolution proteomics (LC-MS/MS)
b) Genomic analysis of the variable region (V-gene) from antibody-encoding B cells by Next Generation Sequencing (NGS) that is used as an individual sequence database to interpreting spectra obtained from the proteomic arm
c) Data analysis using advanced bioinformatics tools to generate a immune-profile map of the immune response
We focus on the following research targets:
Maternal-infant antibody repertoires: towards programming the future health of neonates
The maternal immune system during pregnancy and following birth via lactation, generates and transfers antibodies that have a critical role in establishing the future health of the offspring. Despite their importance, little is known about the specific identities, clonality, functionality, and relative concentration of the monoclonal antibodies that comprise the maternal polyclonal antibody pool.
We aim to achieve a conceptual and technological breakthrough in maternal-infant immunity research by profiling the molecular composition, dynamics and attributes of maternal, trans-placental and breastmilk vaccine-specific antibodies
Moreover, we aim to delineate the association of breast milk antibodies with the establishment of the infants gut microbiome
Potential applications:
1) New vaccine designed for pregnancy and trans-placental transfer of vaccine-specific antibodies
2) Passive immunization by therapeutic monoclonal antibodies transferred via the placenta
3) Antibodies as trans-placental carriers for the transfer of drugs during gestation
Drug Monitoring
The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are chronic disorders that cause uncontrolled inflammation in the gastrointestinal tract. Infliximab (IFX) is a chimeric monoclonal antibodies for the treatment of IBD but approximately 40% of patients treated with IFX develop a loss of response (LOR) to the drug as it elicits anti drug antibodies (ADA). Currently, the repertoire of ADA is not known, which is crucial for the understanding of LOR and ADA mechanisms in IBD
We will perform an in-depth analysis of the ADA following treatment with Infliximab. Our results may provide a therapeutic solution for the LOR to IFX treatment
Potential applications:
1) Decoy peptides to divert the humoral response and decrease LOR
2) Modified drug to reduce immunogenicity

Collectively, our proposed omics approach has the potential to be used to address basic immunological questions as well as an application-focused tool for vaccine development, immunodiagnostic discovery, and monoclonal antibody engineering.

Lab page: http://yarivwine.wix.com/yarivwine

About Dr. Yariv wine: https://english.tau.ac.il/profile/yarivwine

Project manager

Adi Elkeles
BD Manager

Project researchers

Yariv Wine
T.A.U Tel Aviv University, Life Sciences
Molecular Microbiology-Biotechnology