Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection

Arunkumar, Govindakarnavar; Devadiga, Santhosha; McElroy, Anita K.; Prabhu, Suresh; Sheik, Shahin; Abdulmajeed, Jazeel; Robin, Sudandiradas; Aswathyraj, Sushama; Jayaram, Anup; Sudheesh, N; Shakir, Muhammed; Kumar, K G Sajeeth; Radhakrishnan, Chandni; Sakeena, Karayil; Vasudevan, Jayasree; Reena, K; Sarita, R L; Klena, John D.; Spiropoulou, Christina F.; Laserson, Kayla F.; Nichol, Stuart T.

doi:10.1093/cid/ciz010

Cited by 28 publications

(23 citation statements)

References 25 publications

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“…Interestingly, a recent study examining B and T cell populations in two survivors of NiV infection in India [31] identified activation of both CD4+ and CD8+ T cells and proliferation (Ki67+) of CD8+ T cells in a response that is similar to that seen in the surviving animal in the study reported here. While the survivor study examined a very limited population (n = 2) and the study reported here identified only a single NHP survivor, the correlations between the human and NHP B and T cell responses is compelling and potentially identifies key correlates of protective immunity.…”

Section: Discussionsupporting

confidence: 76%

Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

Lara¹,

Yu²,

Jahrling³

et al. 2019

PLoS Negl Trop Dis

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The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8 bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and “cytokine storm” are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection.

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Section: Discussionsupporting

confidence: 76%

Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

Lara¹,

Yu²,

Jahrling³

et al. 2019

PLoS Negl Trop Dis

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“…This observation is further supported by studies in a pig model for NiV infection showing substantial activation of CD8 T cells after oral infection with NiV [45]. In line with these preclinical data, humans surviving NiV infection [2] showed significant levels of proliferating (Ki-67+) CD8 T cells, indicating the presence of acute effector cells. These data emphasize that in addition to the humoral immune responses, T cells could be associated with recovery from NiV infection.…”

Section: Discussionsupporting

confidence: 65%

“…Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides. the first time NiV emerged in southern India [2]. Two strains of NiV have been identified, Malaysia and Bangladesh strains, which share 91.8% sequence homology [3].…”

mentioning

confidence: 99%

A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice

Kalodimou

Veit²,

Jany³

et al. 2019

Viruses

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Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA-NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA-NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA-NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides. the first time NiV emerged in southern India [2]. Two strains of NiV have been identified, Malaysia and Bangladesh strains, which share 91.8% sequence homology [3]. NiV causes severe respiratory disease and encephalitis [4][5][6], with average case fatality rates (CFR) of 40-75% [7]. Moreover, long-term neurological sequelae and even relapse of encephalitis are observed in many survivors of infections with both strains of NiV [8][9][10].The natural reservoir of NiV and Hendra virus (HeV) are the fruit bats of the genus Pteropus, which are widely distributed in Asia, Australasia, and parts of Africa [11,12]. Moreover, NiV has a broad species tropism and can cause disease in a many animal species [13][14][15]. NiV can infect humans via several routes, which include the consumption of food contaminated with bat secretions [16], transmission from amplification hosts such as pigs [4], and direct human-to-human transmission between very close contacts [17]. Currently there are no licensed treatments or preventative vaccines available for use in humans, which make the development of effective prophylactic measures imperative.Evidence to date indicates that the Henipavirus glycoprotein G is a highly promising target of virus-neutralizing antibodies to counteract infections with highly pathogenic henipaviruses. The G gly...

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“…Virus clearance from the blood coincided with peak CD8 T cell activation and the appearance of KFDV-specific IgG. Significant CD8 T cell activation was noted during the acute phase of KFD, as has been noted during infection or after vaccination with dengue, yellow fever, tick-borne encephalitis, Nipah, Ebola, and Lassa viruses, among others [14][15][16][17][18][19] . Activated (Ki67 +) CD8 T cells expressed high levels of acute effector markers PD-1 and CLTA-4 and cytotoxic molecules such as granzyme B and perforin, as well as low levels of Bcl-2, and CD45RA, suggesting that these effector cells were recruited from the naïve population via antigen-specific activation.…”

Section: Discussionmentioning

confidence: 57%

Dynamics of human B and T cell adaptive immune responses to Kyasanur Forest disease virus infection

Devadiga

McElroy

Prabhu

et al. 2020

Sci Rep

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Kyasanur Forest disease (KFD) is a tick-borne, acute, febrile viral illness endemic in southern India. No major studies have been done to understand the adaptive immune response during KFDV infection in humans. In this study, KFDV-positive patients were prospectively enrolled, and repeated peripheral blood collections were performed. Clinical and virologic characterization of these samples is reported along with phenotypic analysis of cellular immunity and quantitation of humoral immunity. We noted robust T and B cell responses, particularly of CD8 T cells, during KFDV infection in most of the patients. Virus clearance from the blood coincided with peak CD8 T cell activation and the appearance of KFDV-specific IgG. Increased frequency of plasmablasts and very few activated B cells were observed in the acute phase of KFD infection. Notably, only humoral immunity and activated B cell frequency in the acute phase correlated with prior KFDV vaccination, and only with 2 or more doses. This novel work has implications in KFD vaccine research as well as in understanding the pathogenesis.

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Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection

Cited by 28 publications

References 25 publications

Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice

Dynamics of human B and T cell adaptive immune responses to Kyasanur Forest disease virus infection

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