MAJOR ARTICLE 1752 • CID 2019:69 (15 November) • Arunkumar et al Clinical Infectious Diseases Received 15 October 2018; editorial decision 20 December 2018; accepted 4 January 2019; published online January 7, 2019. Correspondence: G. Arunkumar, Manipal Centre for Virus Research, Manipal Academy of Higher Education (deemed to be university), Manipal, Karnataka State, India (arun.kumar@manipal.edu). Clinical Infectious Diseases ® 2019;69(10):1752–6 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciz010 Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection Govindakarnavar Arunkumar, 1 Santhosha Devadiga, 1 Anita K. McElroy, 2,3 Suresh Prabhu, 1 Shahin Sheik, 1 Jazeel Abdulmajeed, 1 Sudandiradas Robin, 1 Aswathyraj Sushama, 1 Anup Jayaram, 1 Sudheesh Nittur, 1 Mohammed Shakir, 1 Keeriyatt Govindan Sajeeth Kumar, 4 Chandni Radhakrishnan, 4 Karayil Sakeena, 5 Jayasree Vasudevan, 5 Kalathil Joseph Reena, 5 Ragini Lohithakshan Sarita, 5 John D. Klena, 2 Christina F. Spiropoulou, 2 Kayla F. Laserson, 2 and Stuart T. Nichol 2 1 Manipal Centre for Virus Research, Manipal Academy of Higher Education, Karnataka, India; 2 Centers for Disease Control and Prevention, Atlanta, Georgia; 3 Department of Pediatrics, University of Pittsburgh, Pennsylvania; and 4 Government Medical College, Kozhikode, Kerala, and 5 Directorate of Health Services, Government of Kerala, Thiruvananthapuram, India Background. Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. Methods. Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used fow cytome- try to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specifc immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results. Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67 + ) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profle of acute efector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. Tese individuals developed detectable NiV-specifc IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specifc IgG and coincided with the peak of activated CD8 T cells. Conclusions. We describe for the frst time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with efector characteristics, activated CD4 T cells were less prominent. Keywords. Nipah virus; immune response; NVD. Nipah virus disease (NVD) is an emerging zoonotic viral disease with very high mortality [1]. Since its first recognition in 1998 in Malaysia [2], Nipah virus (NiV) has been frequently detected in Bangladesh [3], and has been reported in West Bengal in India in 2001 and 2007 [4, 5]. In 2018, it caused an outbreak in Kerala, south India [6]. The World Health Organization has identified NiV as 1 of the 10 potential causes of imminent public health emergencies of international concern and included it as a po- tential candidate for vaccine development in its research and development blueprint [7]. To date, a total of 596 cases of human NiV infection have been reported globally, with 347 deaths [2, 8–10]. However, little information is available on the human immune response to NiV infection, most of it, limited to innate and humoral im- mune responses [11]. No information exists on cellular immune responses to NiV in humans [11], although some reports de- scribe cell-mediated and humoral immune responses to NiV in naturally infected swine [12] and experimentally infected mon- keys [13]. In this report, we investigated the recent NiV outbreak in Kerala, India. Of the 18 patients with laboratory-confrmed NVD, 16 died from the disease, whereas 2 recovered without apparent sequelae. Te surviving patients provided an oppor- tunity to study cell-mediated and humoral immune responses against NiV infection in humans during the acute and conva- lescent phases of illness. Tis would help to understand the di- sease pathogenesis and to design disease prevention and control strategies including vaccine development. MATERIALS AND METHODS Human Subjects Research and Biosafety Precautions This study was done as part of the public health response to an NiV outbreak in Kerala. 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