Genetic basis for B and T cell recognition and function – Gunilla Karlsson Hedestam Group

Our research focuses on adaptive immune responses and qualitative properties of B- and T-cell repertoires. A specific interest in the group is to understand individual variation in germline V, D and J genes and how this influences antigen-specific responses in the context of infection, vaccination and autoimmunity.

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Gunilla Karlsson Hedestam Group 2024

Research Description

Genetic basis for B and T cell recognition and function

Our research focuses on qualitative aspects of B and T cell receptor (BCR and TCR) repertoires and their genetic basis. While many of our projects address questions related to B cell biology and antibody specificities, the techniques we have developed are suitable for studies of both BCR and TCR repertoires. For example, we have a special interest in gdT cells and how variation in the genes that encode these receptors influence biological outcomes. 

BCRs and TCRs assemble through somatic rearrangements of a set of germline-encoded V, D and J genes. Because there is considerable inter-individual variation in the V, D and J genes in outbred species, we developed two techniques that allow highly precise typing of these genes. One technique, IgDiscover, uses expressed IgM repertoires for germline allele inference while the other technique, ImmuneDiscover, uses a high throughput multiplex targeted genomic PCR approach. For each method we developed specialized software for data analysis. Using these techniques and analysis tools, we have demonstrated extensive variation in germline BCR and TCR V, D and J allele content between individuals and populations. 

The development of these genotyping techniques is a major technical advance that enables individualized genotyping to become a standard element of high-quality immunological studies in both humans and experimental animals. Furthermore, the high throughput technique ImmuneDiscover allows us to study adaptive immune receptor gene variation in thousands of individuals at the same time, opens new possibilities for disease association studies, diagnostics, precision medicine and vaccine design.

In several of our B cell-focused projects, we define anti-viral antibody responses at the clonal level by single-cell sorting memory B cells for sequence analysis of antibody V(D)J transcripts for isolation and characterization (functional and structural) of antigen-specific monoclonal antibodies. We also apply next generation sequencing to analyze expressed BCR repertoires to trace specific antibody lineages to understand their persistence and levels of expansion and affinity maturation in different immune compartments. The development of a high throughput method for Individualized Single Cell Analysis of Paired Expressed antigen receptors, ISCAPE-seq, has greatly accelerated the speed by which we can perform these projects, and we are routinely isolating monoclonal antibodies against a variety of target antigens.

IgDiscover

IgDiscover

IgDiscover

The production of individualized genetic profiles of B cell receptor and T cell receptor V, D and J genes is central in many areas of research and for personalized medicine applications. While standard deep sequencing approaches do not achieve necessary coverage to profile these genes, the use of IgDiscover and related technologies, can achieve this. Recent developments of the IgDiscover pipeline include tools for high throughput genotyping and haplotype analysis. Click here to visit IgDiscover.

VDJ Databases

Human TCR VDJ database

Human TCR VDJ database

Population-based human V, D and J germline gene sequences for TRA, TRD, TRB and TRG.

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Publications

Selected publications

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Funding

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Funding

We gratefully receive financial support for our research from several organizations, currently from:

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Postal address

Karolinska Institutet
Department of Microbiology, Tumor and Cell Biology
171 77 Stockholm

Visiting address (visitors, couriers, etc.)

Karolinska Institutet
Biomedicum, C7
Solnavägen 9
171 65 Solna

Delivery address (goods, parcels, etc.)

Tomtebodavägen 16
171 65 Solna

Where to find us

Karolinska Institutet, Biomedicum, Solnavägen 9

Research projects

Population studies to characterize adaptive immune receptor germline gene variation

We have developed two main novel techniques, IgDiscover and ImmuneDiscover, which we use to characterize the highly complex loci spanning the BCR and TCR genes. These gene regions are large (up to around 1 million bp per locus) and they comprise several hundred variable (V), diversity (D) and junctional (J) genes, which rearrange in a combinatorial manner to form one unique receptor per nascent B or T cell. Repertoires of BCRs and TCRs display vast antigen recognition capacities with an estimated >109 different receptors present in each person at any given time. Thus, V, D and J genes are key building blocks of BCRs and TCRs and central components of the adaptive immune system. Yet, the variation of V, D and J genes in the human population has remained poorly defined as these gene regions are not covered by conventional whole genome sequencing methods that are based on short reads, which cannot accurately assemble sequences over highly repetitive regions.

In this project, we are characterizing genetic diversity in adaptive immune receptor genes in human cohorts comprising individuals of different population ancestries, focusing initially on BCR and TCR V, D and J genes with the aim to later extend to constant genes and other immune genes. These efforts allow the production of improved genetic databases and provide information about the frequency of alleles present in different populations. In parallel, we apply similar approaches to characterize adaptive immune receptor genes in several non-human primate species for which high-quality genetic databases are lacking. By applying these methods, we obtain highly detailed information about polymorphisms and structural variations in these genes, allowing studies of how the V, D, and J germline allele content influences the establishment of antigen-specific adaptive immune responses.

References

Archaic humans have contributed to large-scale variation in modern human T cell receptor genes.
Corcoran M, Chernyshev M, Mandolesi M, Narang S, Kaduk M, Ye K, Sundling C, Färnert A, Kreslavsky T, Bernhardsson C, Larena M, Jakobsson M, Karlsson Hedestam GB
Immunity 2023 Mar;56(3):635-652.e6

Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.
Pushparaj P, Nicoletto A, Sheward DJ, Das H, Castro Dopico X, Perez Vidakovics L, Hanke L, Chernyshev M, Narang S, Kim S, Fischbach J, Ekström S, McInerney G, Hällberg BM, Murrell B, Corcoran M, Karlsson Hedestam GB
Immunity 2023 Jan;56(1):193-206.e7

Addressing IGHV Gene Structural Diversity Enhances Immunoglobulin Repertoire Analysis: Lessons From Rhesus Macaque.
Kaduk M, Corcoran M, Karlsson Hedestam GB
Front Immunol 2022 ;13():818440

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.
Corcoran MM, Phad GE, Vázquez Bernat , Stahl-Hennig C, Sumida N, Persson MA, Martin M, Karlsson Hedestam GB
Nat Commun 2016 12;7():13642

Rhesus and cynomolgus macaque immunoglobulin heavy-chain genotyping yields comprehensive databases of germline VDJ alleles.
Vázquez Bernat N, Corcoran M, Nowak I, Kaduk M, Castro Dopico X, Narang S, Maisonasse P, Dereuddre-Bosquet N, Murrell B, Karlsson Hedestam GB
Immunity 2021 02;54(2):355-366.e4

High-Quality Library Preparation for NGS-Based Immunoglobulin Germline Gene Inference and Repertoire Expression Analysis.
Vázquez Bernat N, Corcoran M, Hardt U, Kaduk M, Phad GE, Martin M, Karlsson Hedestam GB
Front Immunol 2019 ;10():660

Studies of anti-viral B cell responses through isolation of mAbs and deep repertoire sequencing

B cell responses are the basis by which almost all effective anti-viral vaccines provide protection against infection and disease. Vaccines are still lacking for many human pathogens and in other cases they exist, but do not provide sufficiently broad or long-lasting responses. A robust understanding of B cell biology is needed to develop broadly protective vaccines that provide durable antibody responses. 

Comprehensive analyses of B cell lineages engaged by a specific antigen during infection or immunization, and analysis of how such responses develop over time, are topics of specific interest. We focus particularly on neutralizing anti-viral antibodies and their targets. Characterization of vaccine-induced monoclonal antibodies combined with analysis of polyclonal plasma samples and deep sequencing of antibody repertoires expressed by different B cell populations provide a rich source of information. By sorting antigen-specific B cell populations by flow cytometry and sequencing large numbers of paired heavy and light chains using the ISCAPE-seq method, we can make rapid progress to identify interesting antibody specificities against a range of targets. The questions we are particularly interested in are how antibody responses mature over time, how the clonal dynamics of the response changes following recall stimulation, and qualitative differences between the peripheral memory B cell compartment and the bone marrow plasma cell repertoire against a given antigen.

By combining mAb isolation with repertoire sequencing and antibody lineage studies, we can identify somatic variants, allowing the generation of large family trees for each antibody lineage. From such trees, variants of interest can be selected for expression and functional analyses, allowing the identification of antibodies with improved properties. Moreover, lineage tracing provides information about biological properties of the response, such as whether a given lineage is found in long-lived B cell compartments and thus, contributes to long-lived memory. We also ask if specific germline immunoglobulin alleles are required for certain types of antibody specificities and if so, how this influences responses in different population groups.

References

Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques.

Mandolesi M, Das H, de Vries L, Yang Y, Kim C, Dhinakaran M, Castro Dopico X, Fischbach J, Kim S, Guryleva MV, Àdori M, Chernyshev M, Stålmarck A, Hanke L, McInerney GM, Sheward DJ, Corcoran M, Hällberg BM, Murrell B, Karlsson Hedestam GB.

Nat Commun. 2024 Jul 27;15(1):6338. 


Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.

Sheward DJ, Pushparaj P, Das H, Greaney AJ, Kim C, Kim S, Hanke L, Hyllner E, Dyrdak R, Lee J, Dopico XC, Dosenovic P, Peacock TP, McInerney GM, Albert J, Corcoran M, Bloom JD, Murrell B, Karlsson Hedestam GB, Hällberg BM.

Cell Rep Med. 2024 Jun 18;5(6):101577. 

 

Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages.
Chernyshev M, Sakharkar M, Connor RI, Dugan HL, Sheward DJ, Rappazzo CG, Stålmarck A, Forsell MNE, Wright PF, Corcoran M, Murrell B, Walker LM, Karlsson Hedestam GB
Nat Commun 2023 Apr;14(1):2249

Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.
Pushparaj P, Nicoletto A, Sheward DJ, Das H, Castro Dopico X, Perez Vidakovics L, Hanke L, Chernyshev M, Narang S, Kim S, Fischbach J, Ekström S, McInerney G, Hällberg BM, Murrell B, Corcoran M, Karlsson Hedestam GB
Immunity 2023 Jan;56(1):193-206.e7

Vaccination induces HIV broadly neutralizing antibody precursors in humans.
Leggat DJ, Cohen KW, Willis JR, Fulp WJ, deCamp AC, Kalyuzhniy O, Cottrell CA, Menis S, Finak G, Ballweber-Fleming L, Srikanth A, Plyler JR, Schiffner T, Liguori A, Rahaman F, Lombardo A, Philiponis V, Whaley RE, Seese A, Brand J, Ruppel AM, Hoyland W, Yates NL, Williams LD, Greene K, Gao H, Mahoney CR, Corcoran MM, Cagigi A, Taylor A, Brown DM, Ambrozak DR, Sincomb T, Hu X, Tingle R, Georgeson E, Eskandarzadeh S, Alavi N, Lu D, Mullen TM, Kubitz M, Groschel B, Maenza J, Kolokythas O, Khati N, Bethony J, Crotty S, Roederer M, Karlsson Hedestam GB, Tomaras GD, Montefiori D, Diemert D, Koup RA, Laufer DS, McElrath MJ, McDermott AB, Schief WR
Science 2022 Dec;378(6623):eadd6502

Structurally related but genetically unrelated antibody lineages converge on an immunodominant HIV-1 Env neutralizing determinant following trimer immunization.
Aljedani SS, Liban TJ, Tran K, Phad G, Singh S, Dubrovskaya V, Pushparaj P, Martinez-Murillo P, Rodarte J, Mileant A, Mangala Prasad V, Kinzelman R, O'Dell S, Mascola JR, Lee KK, Karlsson Hedestam GB, Wyatt RT, Pancera M
PLoS Pathog 2021 Sep;17(9):e1009543

High-resolution definition of vaccine-elicited B cell responses against the HIV primary receptor binding site.
Sundling C, Li Y, Huynh N, Poulsen C, Wilson R, O'Dell S, Feng Y, Mascola JR, Wyatt RT, Karlsson Hedestam GB
Sci Transl Med 2012 Jul;4(142):142ra96

Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign.
Tran K, Poulsen C, Guenaga J, de Val N, de Val Alda N, Wilson R, Sundling C, Li Y, Stanfield RL, Wilson IA, Ward AB, Karlsson Hedestam GB, Wyatt RT
Proc Natl Acad Sci U S A 2014 Feb;111(7):E738-47

Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.
Martinez-Murillo P, Tran K, Guenaga J, Lindgren G, Àdori M, Feng Y, Phad GE, Vázquez Bernat N, Bale S, Ingale J, Dubrovskaya V, O'Dell S, Pramanik L, Spångberg M, Corcoran M, Loré K, Mascola JR, Wyatt RT, Karlsson Hedestam GB
Immunity 2017 05;46(5):804-817.e7

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.
Phad GE, Pushparaj P, Tran K, Dubrovskaya V, Àdori M, Martinez-Murillo P, Vázquez Bernat N, Singh S, Dionne G, O'Dell S, Bhullar K, Narang S, Sorini C, Villablanca EJ, Sundling C, Murrell B, Mascola JR, Shapiro L, Pancera M, Martin M, Corcoran M, Wyatt RT, Karlsson Hedestam GB
J Exp Med 2020 02;217(2):

 

Role of adaptive immune receptor gene variation in autoimmune diseases

Human adaptive immune responses to foreign antigens and auto-antigens vary greatly between individuals both in terms of magnitude and quality. Stochastic processes that occur during recombination of germline V, D and J genes, through the addition or trimming of non-templated nucleotides at the VDJ junctions are a known source of variability; however, how heritable polymorphisms and structural variations in BCR and TCR germline genes influence adaptive immune responses remain poorly understood. Genetic predispositions are known for several immune-mediated diseases. Specific MHC class II alleles are associated with the development of several autoimmune conditions but the potential contribution of germline-encoded variations in BCR or TCR genes have so far not been systematically investigated. 

Our high throughput technique for adaptive immune receptor genotyping, ImmuneDiscover, offers new possibilities to investigate the roles of BCR and TCR polymorphisms in large populations and disease cohorts. The current version of ImmuneDiscover is based on targeted genomic sequencing of over 400 genetic elements and utilizes a software to enable analyses of these complex genomic loci, at an individualized level. ImmuneDiscover can be used in a high throughput manner for personalized immune profiling of large numbers of individuals (>1000) from disease cohorts where DNA samples are available. We are currently using this technique to identify potential associations between germline-encoded polymorphisms in adaptive immune receptor genes and outcomes in patients diagnosed with autoimmune conditions in collaboration with several groups at the Karolinska Institutet as well as with international groups such as those belonging to the ID-DarkMatter-NCD Project consortium, https://www.darkmatter-project.eu/

 

Summary of lab activities

Gunilla Karlsson Hedestam Group

Resources

IgDiscover

IgDiscover

The computational tool, IgDiscover, allows the production of individualized genetic profiles of adaptive immune receptor V, D and J genes, which is central for many areas of research and personalized medicine applications.

Macaque IG VDJ database

Macaque IG VDJ database

This database incorporates IGHV, IGHJ and IGHD sequences from four subgroups of macaques, namely Indian and Chinese origin Rhesus macaques and Indonesian and Mauritian origin Cynomolgus macaques.

Human TCR VDJ database

Human TCR VDJ database

Population-based human V, D and J germline gene sequences for TRA, TRD, TRB and TRG.

Popular science articles

A better picture of the immune response to COVID-19 

When the corona pandemic was a fact in March 2020, Gunilla Karlsson Hedestam, professor of ­vaccine ­immunology at Karolinska Institutet, already had a good idea of how viruses and anti-viral immune ­responses ­generally behave.

Read the article from 2024 on Erling-Perssons stiftelses webb page

Unik katalog över genvariationer ska ge mer precisa läkemedel

Genom att kartlägga immunsystemets gener på djupet vill Gunilla Karlsson Hedestams forskargrupp öka kunskapen kring det mänskliga immunförsvaret. Syftet är att skapa bättre diagnostik och nya terapier för patienter i hela världen. 

Läs artikeln från 2024 på Knut och Alice Wallenbergs stiftelses webbsida 

New approaches to investigating diversity in adaptive immune receptor genes

Hundreds of genes recombine in a combinatorial manner to make B- and T-cell receptors, which are integral to the adaptive immune system. In ImmuneDiversity, a project funded by an ERC Advanced grant, the group is investigating human inter-individual diversity in B- and T-cell receptors genes to obtain an improved understanding of disease susceptibility, as Professor Gunilla Karlsson Hedestam explains in this article in EU Research, Autumn 2023 vol. (35), pp. 14 -16.

Read the article in EU Research

Stor variation i generna som kodar för människans T-cellsreceptorer

Vår kunskap om människans arvsmassa blir allt större tack vare snabbare och bättre metoder att sekvensera DNA. Ju fler personer vars DNA analyseras desto bättre förstår vi vilka regioner av arvsmassan som uppvisar stor variation mellan olika personer. Professor Gunilla Karlsson Hedestam och hennes grupp på Karolinska Institutet visade nyligen att generna som kodar för T-cellernas antigen-receptorer uppvisar exceptionellt stor variation. Detta kan ha betydelse för att förstå orsaker till immunmedierade sjukdomar, till exempel inom neurologin, skriver författaren i Neurologi i Sverige no 2, 2023.

Läs artikeln i Neurologi i Sverige

Former PhD students

Åsa Hidmark

2007

Opponent: Bruce Beutler

Åsa defended her PhD in 2007 after which she received the Jonas Söderqvist’s Prize for basic research in virology and immunology. Åsa moved on to a post-doctoral position at the University of Heidelberg in Germany, where she is now active as a senior research scientist in the field of immunology and diabetes.

Mattias Forsell

2008

Opponent: Quentin Sattentau

Mattias defended his PhD in 2008. Part of his doctoral research was carried out at the National Institutes of Health in Washington. After this, he received an Early career investigator AMFAR award for post-doctoral work, which was carried out at Karolinska Institutet. He recently obtained a position as Assistant Professor at Umeå University where he now leads his own research group.

Pia Dosenovic

2012

Opponent: Michael McHeyzer-Williams

Pia defended her PhD in 2012 after which she obtained 3 years of funding from the Swedish Research Council to pursue a post-doc at the Rockefeller University in New York. After several years as a productive member of the Nussenzweig laboratory, she is now back at KI to establish her own research group.

Christopher Sundling

2012

Opponent: Robin Weiss

Christopher defended his PhD in 2012 and in the last year of his studies he was awarded the Dimitris N. Chorafas Foundation Prize. He subsequently also received the Jonas Söderqvist’s Prize for basic research in virology and immunology and Sven Gard’s prize for best thesis in virology. He then moved on to a post-doc position in the Brink laboratory at the Garvan Institute in Sydney and returned in 2017 to establish his own group at the Department of Medicine, Solna as an Assistant Professor.

Paola Martinez Murillo

2017

Opponent: Leo Stamatatos

Paola defended her PhD in May of 2017. During her doctoral education she collaborated closely with scientists at the Scripps Research Institute in La Jolla and she spent a month as a visiting student at the Rockefeller University. An additional initiative she took was to teach Immunology to young students in Colombia, two summers in a row. Her Immunity paper published just before her PhD defense received “Best paper of the year” at MTC 2017. Paola is now a senior postdoc evaluating extracellular vesicles immune modulation and translational potential in atopic dermatitis in the Mantel lab in Davos, Switzerland.

Martina Soldemo

2017

Opponent: Klaus Überla

Martina defended her PhD in October of 2017 after a productive time as a doctoral student. In addition to her own projects, she was instrumental to many collaborations both within and outside the lab and she contributed enthusiastically to teaching at both the undergraduate and post-graduate level at KI. She is currently a Scientific Project Manager in Immunology at the Janssen Pharmaceutical Companies of Johnson & Johnson in Stockholm.

Ganesh Phad

2018

Opponent: Stephen Quake

Ganesh defended his PhD in June 2018. During his doctoral studies, he applied a broad set of techniques to study B cell responses and immunization-induced monoclonal antibodies. He was instrumental in setting up Next Generation Sequencing methodology for analyses of antibody repertoires and, together with Martin Corcoran in the group and computational scientist Marcel Martin, developed the broadly applicable IgDiscover tool. Ganesh is currently a post-doctoral fellow in the laboratory of Antonio Lanzavecchia in Switzerland.

Néstor Vazquez Bernat

2019

Opponent: Scott Boyd

Néstor defended his PhD in December 2019 with a thesis focusing on antibody repertoire sequencing and germline gene identification in humans and macaques. He worked closely with his co-supervisor Martin Corcoran to optimize protocols for IgM library production for germline inference and with methods to validate novel alleles identified with the IgDiscover software. His recent paper in Immunity describes a comprehensive database of rhesus and cynomolgus macaque antibody germline alleles, now publicly available (see above). Néstor is currently working with immune repertoire sequencing at ENPICOM in the Netherlands.

Sharesta Khoenkhoen

2020

Opponent: David Tarlinton

Sharesta defended her PhD thesis in August 2020. During her doctoral studies, Sharesta studied B cell defects in mice lacking an NFkB regulator, IKBNS. The most striking phenotype of IKBNS-deficient mice is that they fail to develop B-1 cells while follicular B cells (FoB cells) develop and are present at normal frequencies. Sharesta demonstrated that while FoB cells present in IKBNS-deficient mice, they are dysfunctional in their ability to differentiate into plasma cells. Sharesta investigated key steps in this process to pinpoint the defect. After leaving the lab, she took up a position as a TCR discovery scientist at T-knife Therapeutics in Berlin.

Pradeepa Pushparaj

2023

Opponent: Penny Moore

Pradeepa defended her PhD in May 2023. During her studies, Pradeepa gained deep expertise in techniques used to dissect B cell responses at the clonal level to investigate qualitative features of antibody responses elicited by infection or vaccination. By isolating monoclonal antibodies from antigen-specific memory B cells, and combining this with antibody engineering, functional studies, and lineage tracing in deep-sequenced repertoire data, she investigated questions related to antibody affinity maturation and the development of long-lived memory B cells and plasma cells. In her Immunity paper published in 2023, she applied personalized antibody VDJ genotyping to a cohort of SARS-CoV-2 convalescent individuals and showed that germline-encoded polymorphisms can influence the type of antibody response made, illustrating a functional role for antibody germline gene variation in humans.

Marco Mandolesi

2023

Opponent: Bob Seder

Marco defended his PhD in February 2023. His thesis work covered a broad range of topics in immunology, including individualized typing of human and macaque T- and B-cell receptor germline genes, identification and validation of novel alleles, immunization studies and characterization of elicited adaptive immune responses, isolation of monoclonal antibodies and B cell lineage tracing to follow the evolution of the antibody response. His time as a doctoral student in the lab overlapped with the COVID-19 pandemic and he was able to quickly refocus his efforts to contribute to the understanding of SARS-CoV-2-directed neutralizing antibody responses. He also contributed greatly to a paper on TCR germline gene polymorphisms published in Immunity just before his PhD defense. He is highly skilled in immune repertoire analysis and is currently staying on as a post-doctoral scientist to wrap up projects and help supervise new members of the laboratory.

Sanjana Narang

2024

Opponent: Ludvig Sollid

Sanjana defended her PhD in March 2024. Her doctoral work focused on human immunogenetics and the development of wet lab techniques and analysis tools for individualized genotyping of B and T cell receptor (BCR and TCR) germline alleles. She worked extensively on data generated by IgDiscover and together with her co-supervisor Martin Corcoran, she developed the CoreCount genotyping tool. She contributed greatly to the development and validation of the high throughput genotyping tool, ImmuneDiscover and its application to the thousand genome samples (1KGP) and other cohorts to understand variation in the immunoglobulin loci in humans from different population ancestries. In addition to her contributions to the analysis of genetic variations in the human IGH locus, she developed the technique for highly precise analysis of the IGK and IGL loci, work that she is currently finalizing. Sanjana is currently staying on as a post-doctoral scientist to complete projects and collaborate with other members of the group.

Co-supervisor

Gunilla Karlsson Hederstam has also been co-supervisor for:

  • Cornelia Gujer, 2011
  • Kai Eng, 2012
  • Lina Josefsson, 2013
  • Marc Panas, 2014
  • Lotta Pramanik Sollerkvist, 2014
  • Faezzah Baharom 2016
  • Katrin Habir, 2018
  • Julian Stark, 2020
  • Sebastian Ols, 2022
  • Uta Hardt, 2022

Sheward Lab

The development of effective vaccines against HIV and other highly variable viruses for which there are no licensed vaccines is a major global health priority. The ability to pre-emptively vaccinate against clades of viruses with pandemic potential could also prevent another global pandemic.

Research focus

Next-generation mRNA vaccines

Using state-of-the-art mRNA delivery, we are developing and characterizing next-generation vaccines aiming to elicit broadly neutralizing antibodies that could protect against highly variable viruses or prevent the next pandemic. A current research focus is on the antibody response to vaccine ‘cocktails’.

Adapting the mechanisms and pathways used by viruses to manipulate host cell biology

Viruses are experts at the manipulation of host cells. By characterizing how viruses modify host cell biology we aim to identify mechanisms and pathways that can be exploited to improve mRNA vaccines, or treat other human diseases. A current research focus is on how viruses enhance the translation of their own mRNA, and the adaptation and refinement of these mechanisms to improve mRNA delivery.

Monitor the immune response to infection and vaccination

Using virus neutralization assays we characterize the antibody response following infection and vaccination – using this to inform both vaccine design and public health policy.  Over the course of the COVID-19 pandemic we have been monitoring the neutralizing antibody response to SARS-CoV-2 variants at the population level in Sweden.

 

Read more about Sheward Lab here

Contact

Profile image

Daniel Sheward

Assistant Professor
Keywords:
Adaptive Immunity Antibodies, Monoclonal Bioinformatics (Computational Biology) (Applications at 10610) Cell and Molecular Biology Immunogenetics Show all
Content reviewer:
Gunilla Karlsson Hedestam
Sara Lidman
31-03-2025