SUPR
Transciptomic profiling and BCR immune repertoire analysis following vaccination in healthy and immunocompromised individuals.
Dnr:

sens2021598

Type:

SNIC SENS

Principal Investigator:

Karin Loré

Affiliation:

Karolinska Institutet

Start Date:

2021-11-25

End Date:

2024-12-01

Primary Classification:

30110: Immunology in the medical area

Webpage:

Allocation

  • Castor /proj/nobackup at UPPMAX: 10000 GiB
  • Cygnus /proj/nobackup at UPPMAX: 10000 GiB
  • Castor /proj at UPPMAX: 2000 GiB
  • Cygnus /proj at UPPMAX: 2000 GiB
  • Bianca at UPPMAX: 2 x 1000 core-h/month

Abstract

Immune repertoire sequencing is creating a new promising research field which can help the understanding and development of better vaccines. There is currently limited understanding of B cell receptor (BCR) repertoires after vaccination in immunodeficient populations, and how the mechanisms of vaccine-induced selection and diversification of B cell populations may differ in these populations relative to immunocompetent individuals. We aim to decipher these phenomena in the context of responses to SARS-CoV-2 mRNA vaccination in hematopoetic stem cell transplant recipients, examining the influence of time elapsed between transplantation and vaccination as well as the presence or absence of chronic graft-versus-host disease (GvHD). Our samples derive from an ongoing phase IV clinical trial evaluating Pfizer/BioNTech mRNA vaccine b62BNTb2. In total, we have performed Immunoglobulin repertoire sequencing (Ig-Seq) for 20 of these individuals following vaccination. From these data we aim to capture differences in the immune repertoires of vaccinated HSCT patients who are early or late after their transplantation and compare this to healthy immunocompetent vaccinees. Additionally, we aim to understand early immune events after mRNA vaccination and their influence on the development of protective responses. To this end we conducted a clinical trial testing the b62BNTb2 vaccine in healthy individuals. We have generated longitudinal RNA-Seq data from 10 individuals at multiple timepoints before and early after each of two vaccine doses, to examine early transcriptomic changes that reflect the inflammatory response induced by mRNA injection. With these data we hope to understand how early inflammatory responses shape characteristics of vaccine-induced immunity. In order to analyze the complex data generated, we will use custom R and python programming scripts. Finally, with these data we hope to gain insights into how mRNA vaccines modulate innate and adaptive immune responses in different groups.