Comparative immune profiling in survivors of the 2023 Nipah outbreak in Kerala state, India

Abstract Immune profiling of Nipah virus (NiV) infection survivors is essential for advancing our understanding of NiV pathogenesis, improving diagnostic and therapeutic strategies, and guiding public health efforts to prevent future outbreaks. There is currently limited data available on the immune response to NiV infection. We aimed to elucidate the specific immune mechanisms involved in protection against NiV infection by analyzing the immune profiles of survivors of the Nipah outbreak in Kerala, India 2023. Immune cell populations were quantified and compared between survivors (up to 4 months post onset day of illness) and healthy controls. Statistical analysis was performed to explore associations between immune profiles and clinical outcomes. Immune signatures common to all three cases were: a heretofore undescribed persistent lymphopenia including the CD4+ Treg compartment with the relative expansion of memory Tregs; trends indicative of global leukopenic modulation were observed in monocytes and granulocytes including an expansion of putatively immunosuppressive low‐density granulocytes described recently in the context of severe COVID‐19; altered mucosal homing with respect to integrin beta‐7 (ITGB7) expressing subsets; increased mobilization of activated T‐cells (CD4+ and CD8+) and plasmablasts in the early phase of infection. Comparative analysis based on clinical presentation and outcome yielded lower initial viremia, increased activated T‐cell responses, expanded plasmablasts, and restoration of ITGB7 expressing CD8+ T‐cells as possible protective signatures. This longitudinal study delineates putative protective signatures associated with milder NiV disease. It emphasizes the need for the development of immunotherapeutic interventions such as monoclonal antibodies to blunt early viremia and ameliorate pathogenesis.