Use of ISCAPE to identify population vulnerabilities in the influenza antibody response

PI(s)/Head responsible for the resource:

Gunilla Karlsson Hedestam

Host organisation(s):

Karolinska Institutet

Resource description:

Human adaptive immune responses to viruses vary greatly between individuals, both in terms of magnitude and quality, but the reasons underpinning these differences are not well understood. The complexity of our response to seasonal viruses, such as influenza, increases during our lifetime as we are exposed to different antigenic variants with varying time intervals, sometime through infection and sometime through vaccination. Thus, while our memory B cell repertoires against circulating viruses change over time, a major determinant is the first encounter with antigen, so-called immunological imprinting. We have shown that the elicitation of a primary antibody response is influenced by host genetics, which may explain why broadly neutralizing antibody responses develop in some people but not in others. Understanding inter-individual differences in antibody responses is of great importance for pandemic preparedness.

Here, we will use ISCAPE (Individualised Single Cell Analysis of Paired Expressed antigen receptors), a technique that couples personalised IG genotyping and high-throughput sequencing of indexed/paired heavy chain and light chain transcripts from antigen-binding memory B cells for computational analyses and monoclonal antibodies (mAb) isolation. We developed ISCAPE as part of our previous PLP-funded project and we utilised it to demonstrate that the HA-specific response is highly individual and that the technique allows rapid isolation of fully human broadly neutralising mAbs. In this project, we will scale up ISCAPE to delineate public and private antibody lineages against both HA and neuraminidase (NA) in donors from the CoVUm cohort, assembled by the Normark/Forsell/Ahlm groups, Umeå University. These studies will improve our understanding of the diversity in the human antibody response to influenza to guide vaccine development. The possibility to tailor booster recommendations to enhance population immunity will improve pandemic preparedness.

Contact information:

Gunilla Karlsson Hedestam
Tumor and Cell Biology (MTC), Department of Microbiology, Karolinska Institutet
Email: Gunilla.Karlsson.Hedestam@ki.se