All Publications


  • Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth. Immunity Wirz, O. F., Kotagiri, P., Haraguchi, E., Röltgen, K., Hunter, M., Craig, E., Afaghani, J., Lee, J. Y., Nielsen, S. C., Hoh, R. A., Pursell, T., Arunachalam, P. S., Manohar, M., Chang, I., Schuetz, J. P., Lam, B., Fernandes, A., Do, E., Smith, D., Ha, B., Liao, L., Najeeb, J., Otrelo-Cardoso, A. R., Ho, C., Wohlstadter, J. N., Sigal, G. B., Jardetzky, T. S., Scott, S. A., Van Slyck, S., Davis, M. M., Pulendran, B., Minshull, J., Pinsky, B. A., Nadeau, K. C., Niemann, C. U., Yang, F., Boyd, S. D. 2026

    Abstract

    The cellular, immunogenetic, and antigenic factors affecting the breadth of viral antigen variants recognized by human antibody responses are poorly defined. We developed highly multiplexed panels of DNA-tagged SARS-CoV-2 antigens from up to 20 viral variants to label and sort 6,262 antigen-binding circulating B cells from previously naive mRNA vaccinees or infected patients, and from deceased organ donor lymphoid tissues, to enable antigen receptor and transcriptome sequencing. Atypical B cells and a subset of class-switched memory cells with evidence of recent germinal center exposure were enriched for antigen binding. In contrast to atypical B cells, post-germinal center B cells showed progressively increasing variant binding breadth and somatic hypermutation over time. Vaccination, compared with infection, preferentially stimulated B cells expressing antibodies with inherently high antigen-binding breadth. This large-scale analysis reveals key determinants of antigen-binding breadth, critical for understanding responses to viral infection and guiding vaccine development against rapidly mutating viruses.

    View details for DOI 10.1016/j.immuni.2026.03.006

    View details for PubMedID 41928519

  • Immunoglobulin germline reference sequences enable investigations and reveal insights into bat-specific immunity. iScience Reers, A. B., Zhan, S., Pursell, T., Reasoner, C., Hodges, N., Lama, T. M., Schountz, T., Frank, H. K. 2025; 28 (12): 113903

    Abstract

    We generated a highly contiguous, annotated genome of the Jamaican fruit bat, Artibeus jamaicensis, including annotated germline immunoglobulin heavy-chain (IGH) and light-chain lambda (IGL) loci to understand bat B cell receptor repertoires. The bat germline shares many structures and features described in human immunoglobulin loci. However, some features are unique to A. jamaicensis, including an expansion of cysteine-rich IGHV genes. To investigate the relationship between the germline IGH locus and expressed B cell receptors (BCRs), we sequenced the BCRs of wild-caught and captive A. jamaicensis, finding an enrichment of IGHV3 and IGHV4 genes. Compared to humans, A. jamaicensis had shorter CDRH3s and lower levels of somatic hypermutation. Our results demonstrate that while immunoglobulin loci are largely conserved between bats and humans, distinct differences exist in the bat germline, highlighting the need for more detailed genetic characterization of these mammals.

    View details for DOI 10.1016/j.isci.2025.113903

    View details for PubMedID 41321632

    View details for PubMedCentralID PMC12664418

  • NOVEL DIAGNOSTIC AND THERAPEUTIC APPROACHES TO ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1A HEMORRHAGIC DISEASE IN A CAPTIVE JUVENILE ASIAN ELEPHANT (ELEPHAS MAXIMUS) JOURNAL OF ZOO AND WILDLIFE MEDICINE Iyer, M. L., Molter, C. M., Flanagan, J. P., Bauer, K. L., Bernardy, R., Hoffman, D., Parkinson, L., Brainard, B. M., Evans, T., Pursell, T., Ling, P. D. 2022; 53 (1): 232-240

    Abstract

    Novel diagnostic and therapeutic methods were utilized in the successful management of severe elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD) in a 1.9-yr-old captive Asian elephant (Elephas maximus). High levels of EEHV1A viremia were detected for 12 d. In addition to established EEHV treatments, therapies included famciclovir-fortified elephant whole blood and plasma, mesenchymal stem cells harvested from elephant umbilical tissue, and aminocaproic acid. Testing conducted to examine the effects of EEHV infection on hemostasis suggested marked intravascular coagulation with decreased plasminogen activity and increased D-dimer concentrations. Thromboelastography was used to assess the efficacy of aminocaproic acid and demonstrated hypofibrinolysis on samples taken after drug administration, as compared with samples from healthy adult Asian elephants. A serological assay for a novel EEHV1A-specific antibody marker (E52) was developed due to lack of seroconversion to a previously established EEHV1A-specific antibody marker (ORFQ) and showed a sustained increase after EEHV-HD illness.

    View details for DOI 10.1638/2021-0096

    View details for Web of Science ID 000771731400027

    View details for PubMedID 35339171

  • Modified vaccinia Ankara expressing EEHV1A glycoprotein B elicits humoral and cell-mediated immune responses in mice PLOS ONE Pursell, T., Clinton, J., Tan, J., Peng, R., Ling, P. D. 2022; 17 (3): e0265424

    Abstract

    Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. To address this goal, we generated a Modified Vaccinia Ankara (MVA) recombinant virus expressing a truncated form of glycoprotein B (gBΔfur731) from EEHV1A, the strain associated with the majority of lethal EEHV cases. Vaccination of CD-1 mice with this recombinant virus induced robust antibody and polyfunctional T cell responses significantly above mice inoculated with wild-type MVA. Although the vaccine-induced T cell response was mainly observed in CD8+ T cell populations, the CD4+ T cell response was also polyfunctional. No adverse responses to vaccination were observed. Overall, our data demonstrates that MVA-gBΔfur731 stimulates robust humoral and cell-mediated responses, supporting its potential translation for use in elephants.

    View details for DOI 10.1371/journal.pone.0265424

    View details for Web of Science ID 000803647900049

    View details for PubMedID 35312707

    View details for PubMedCentralID PMC8936464