New chimeric antibodies turn marmosets into a working KSHV infection model

Kaposi sarcoma-associated herpesvirus (KSHV) has long lacked a dependable animal model, stalling efforts to understand how the virus establishes infection, persists in the body, and drives Kaposi sarcoma in immunocompromised patients. A new study reports that the common marmoset (Callithrix jacchus), a small New World primate, can support systemic KSHV infection—and that a pair of newly developed monoclonal antibodies makes the model far more informative by unmasking active viral replication and salivary shedding. Earlier work had hinted that marmosets could be infected with KSHV, but the reproducibility and practical value of that observation had never been rigorously established.

In the new research, the team first evaluated a tacrolimus-based immunosuppression regimen, delivered both intravenously and orally, in marmosets challenged with the virus. Infection was confirmed in the challenged animals, but the approach was hampered by inconsistent dosing and toxicity, underscoring the need for a more controllable way to modulate the immune system. To overcome those limitations, the researchers developed and validated two novel mouse–marmoset chimeric monoclonal antibodies: anti-CD4, designated TAWA, and anti-CD8, designated OCHO.

These antibodies selectively deplete CD4-positive and CD8-positive T cell subsets, producing an efficient, subset-specific and quantifiable immunosuppressive regimen that was well tolerated by the animals. Across four independent experiments, KSHV established systemic infection in marmosets under both immunocompetent and immunosuppressed conditions. The evidence included viral DNA detectable in peripheral blood mononuclear cells—indicating viremia—measurable seroconversion, and persistence of the virus in tissues.

The most striking result came from the antibody-treated animals. For the first time, marmosets receiving the chimeric antibodies exhibited KSHV shedding in saliva together with lytic replication, the productive phase of the viral life cycle in which new infectious particles are made. That distinction matters for pathogenesis research, because it shows that infection in this model is not merely latent but supports a full, human-like replication cycle.

The chimeric design of TAWA and OCHO is itself a technical contribution, giving researchers a practical immunosuppressive tool that complements tacrolimus-based regimens, which in this species were complicated by dosing inconsistencies and toxicity. With infection, persistence, seroconversion, lytic replication and salivary shedding all demonstrable in the same small primate, the authors argue that the common marmoset now qualifies as a susceptible and translationally relevant non-human primate model for KSHV.

Beyond basic pathogenesis, the validated model opens a path toward applied research. A reproducible in vivo system that recapitulates infection, persistence and disease provides a foundation for preclinical testing of candidate vaccines and therapeutics against KSHV, a virus linked not only to Kaposi sarcoma but also to several other diseases. The study’s findings are limited to controlled challenge experiments in marmosets, and translating the model’s advantages into clinical advances will require further work, but the combination of a susceptible host and a targeted immunosuppression toolkit gives KSHV researchers a resource they have lacked for decades.

Subject of Research: Development of chimeric anti-CD4 and anti-CD8 monoclonal antibodies to validate the common marmoset as a non-human primate model for Kaposi sarcoma-associated herpesvirus infection

Article Title: Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies

Article References: Han, L., Rodriguez, E., Shaw, C., Kurian, J., Capuano, S., Escalante, G. M., Muniraju, M., Jung, K., Mutsvunguma, L. Z., Engelman, K., Jung, J., Ross, C. N., Reidel, I. G., & Ogembo, J. G. (2026). Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies. PLOS Pathogens, 22(10), e1014698. https://doi.org/10.1371/journal.ppat.1014698

Image Credits: AI Generated

DOI: 10.1371/journal.ppat.1014698

Keywords: KSHV, Kaposi sarcoma, marmoset model, monoclonal antibodies, immunosuppression, CD4 T cells, CD8 T cells, lytic replication, salivary shedding, non-human primate, viral pathogenesis, seroconversion