Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies
6 affiliations
- 1Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, California, United States of America
- 2Irell & Manella Graduate School of Biological Sciences of City of Hope, Duarte, California, United States of America
- 3Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
- 4Department of Microbial Sciences in Health, and Global Center for Pathogen and Human Health Research, Cleveland Clinic Research, Cleveland, Ohio, United States of America
- 5MassBiologics, UMass Chan Medical School, Boston, Massachusetts, United States of America
- 6Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, United States of America
Abstract
Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma, a malignancy that primarily affects immunocompromised individuals, and is also linked to multiple other diseases. Progress in understanding KSHV pathogenesis and developing effective vaccines or therapies has been severely limited by the lack of a reliable in vivo model that recapitulates infection, persistence, and disease. Previous work suggested that the common marmoset (Callithrix jacchus), a small New World primate, can support KSHV infection and pathogenesis, but the reproducibility and utility of this model has not been rigorously established. Here, we sought to validate the common marmoset as a non-human primate model for KSHV studies by evaluating viral infection under both immunocompetent and immunosuppressed conditions. We first tested the use of intravenous and oral tacrolimus-based immunosuppression, confirming infection in challenged marmosets but also encountering tacrolimus dosing inconsistencies and toxicity. To overcome these limitations, we developed and validated a targeted immunosuppression approach using two novel mouse–marmoset chimeric monoclonal antibodies, anti-CD4 [TAWA] and anti-CD8 [OCHO], to selectively deplete T cell subsets. Altogether, we demonstrated across four independent experiments that KSHV can establish systemic infection in both immunocompetent and immunosuppressed conditions marmosets, evidenced by viremia in peripheral blood mononuclear cells, detectable seroconversion, and tissue persistence. The chimeric antibodies mediated efficient, subset‑specific depletion of CD4+ and CD8+ T cells and enabled a quantifiable, well‑tolerated immunosuppressive regimen. Moreover, we showed for the first time that monoclonal antibody-treated marmosets exhibit KSHV shedding in saliva and lytic replication, indicating that infection in this model is not merely latent but supports a full, human‑like replication cycle. Together these findings validate the common marmoset as a susceptible and translationally relevant non-human primate for studying KSHV infection and introduce a practical immunosuppressive tool for dissecting viral pathogenesis and immunity in vivo, providing a platform for testing vaccine and therapeutics. Author summary: Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma, a cancer that affects the skin and internal organs, and is associated with several other diseases that primarily occur in people with weakened immune systems. Studying KSHV has been difficult because the virus naturally infects humans, and suitable animal models are limited. Prior studies showed that common marmosets, a small type of monkey, can be experimentally infected with KSHV, but this animal model has remained underdeveloped. To improve this model, we carefully characterized KSHV infection in marmosets and generated new antibody-based tools to temporarily weaken (i.e., immunosuppress) their immune systems. Using these tools, we demonstrated that KSHV establishes long-term infection in both healthy and immunosuppressed marmosets. Importantly, we showed for the first time that immunosuppressed marmosets can shed KSHV virus in their saliva, indicating KSHV is actively replicating, similar to what is seen in infected humans. Our findings validate the marmoset as a relevant model for KSHV infection and provide a valuable platform in which to study viral biology and to evaluate vaccines and potential treatments.
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BibTeX
@article{han2026newly,
title = {{Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies}},
author = {Li Han and Esther Rodriguez and Caitlin Shaw and Joe Kurian and Saverio Capuano and Gabriela M. Escalante and Murali Muniraju and Kyle Jung and Lorraine Z. Mutsvunguma and Kathleen Engelman and Jae Jung and Corinna N. Ross and Ivana G. Reidel and Javier Gordon Ogembo},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014698},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014698},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies
AU - Li Han
AU - Esther Rodriguez
AU - Caitlin Shaw
AU - Joe Kurian
AU - Saverio Capuano
AU - Gabriela M. Escalante
AU - Murali Muniraju
AU - Kyle Jung
AU - Lorraine Z. Mutsvunguma
AU - Kathleen Engelman
AU - Jae Jung
AU - Corinna N. Ross
AU - Ivana G. Reidel
AU - Javier Gordon Ogembo
PY - 2026
DA - 2026/10/26
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014698
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014698
AB - Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma, a malignancy that primarily affects immunocompromised individuals, and is also linked to multiple other diseases. Progress in understanding KSHV pathogenesis and developing effective vaccines or therapies has been severely limited by the lack of a reliable in vivo model that recapitulates infection, persistence, and disease. Previous work suggested that the common marmoset (Callithrix jacchus), a small New World primate, can support KSHV infection and pathogenesis, but the reproducibility and utility of this model has not been rigorously established. Here, we sought to validate the common marmoset as a non-human primate model for KSHV studies by evaluating viral infection under both immunocompetent and immunosuppressed conditions. We first tested the use of intravenous and oral tacrolimus-based immunosuppression, confirming infection in challenged marmosets but also encountering tacrolimus dosing inconsistencies and toxicity. To overcome these limitations, we developed and validated a targeted immunosuppression approach using two novel mouse–marmoset chimeric monoclonal antibodies, anti-CD4 [TAWA] and anti-CD8 [OCHO], to selectively deplete T cell subsets. Altogether, we demonstrated across four independent experiments that KSHV can establish systemic infection in both immunocompetent and immunosuppressed conditions marmosets, evidenced by viremia in peripheral blood mononuclear cells, detectable seroconversion, and tissue persistence. The chimeric antibodies mediated efficient, subset‑specific depletion of CD4+ and CD8+ T cells and enabled a quantifiable, well‑tolerated immunosuppressive regimen. Moreover, we showed for the first time that monoclonal antibody-treated marmosets exhibit KSHV shedding in saliva and lytic replication, indicating that infection in this model is not merely latent but supports a full, human‑like replication cycle. Together these findings validate the common marmoset as a susceptible and translationally relevant non-human primate for studying KSHV infection and introduce a practical immunosuppressive tool for dissecting viral pathogenesis and immunity in vivo, providing a platform for testing vaccine and therapeutics. Author summary: Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma, a cancer that affects the skin and internal organs, and is associated with several other diseases that primarily occur in people with weakened immune systems. Studying KSHV has been difficult because the virus naturally infects humans, and suitable animal models are limited. Prior studies showed that common marmosets, a small type of monkey, can be experimentally infected with KSHV, but this animal model has remained underdeveloped. To improve this model, we carefully characterized KSHV infection in marmosets and generated new antibody-based tools to temporarily weaken (i.e., immunosuppress) their immune systems. Using these tools, we demonstrated that KSHV establishes long-term infection in both healthy and immunosuppressed marmosets. Importantly, we showed for the first time that immunosuppressed marmosets can shed KSHV virus in their saliva, indicating KSHV is actively replicating, similar to what is seen in infected humans. Our findings validate the marmoset as a relevant model for KSHV infection and provide a valuable platform in which to study viral biology and to evaluate vaccines and potential treatments.
SN - 1553-7374
SN - 1553-7366
ER -