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

Abstract

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...

Bats in ecosystems and their Wide spectrum of viral infectious potential threats: SARS-CoV-2 and other emerging viruses

“…Transmission studies in Australia established that NiV could rapidly spread through pigs via oral and parenteral inoculation. Neutralizing antibodies were detectable 10-14 days after infection ( Kalodimou et al, 2019 , Kenmoe et al, 2019 , Ochani et al, 2019 , Shuai et al, 2020 , Singh et al, 2019 ).…”

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination

“…Quantification was carried out using a standard curve based on 10-fold serial dilutions of appropriate control RNA ranging from 10 to 5 copies.Antigen-specific IgG ELISA. SARS-2-S-specific serum IgG titres were measured by enzymelinked immunosorbent assay (ELISA) as described previously(41). Flat bottom 96-well ELISA plates (Nunc MaxiSorp Plates, Thermo Fisher Scientific, Planegg, Germany) were coated with 50 ng/well recombinant 2019-nCoV (COVID-19) S protein (Full Length-R683A-R685A-HisTag, ACROBiosystems, Newark, USA) overnight at 4 °C.…”

Lentiviral Vector Pseudotypes: Precious Tools to Improve Gene Modification of Hematopoietic Cells for Research and Gene Therapy

“…Nipah virus (NV) is a negative-sense single-stranded RNA virus from the genus Henipavirus from the Paramyxoviridae family. It has a very broad tropism and uses protein-based receptors [50,60]. Similar to the MV envelopes, the NV envelopes encode two glycoproteins to allow entry into the cell: the attachment protein (G), which allows the virion attachment to the cellular receptors and the fusion protein (F), which mediate the union of the viral membrane with the cell membrane [49,61,62].…”

“…Recently, several vaccines based on the G glycoprotein of the NV to protect against lethal infections, are evaluated in pre-clinical trials [60], underlining its capacity to induce an immune response. Even though the role of antibodies in immunization against NV infection has been extensively reported, few studies addressed the induction of T-cell immunity.…”

“…Even though the role of antibodies in immunization against NV infection has been extensively reported, few studies addressed the induction of T-cell immunity. Kalodimou et al [60] have recently reported potential epitopes that stimulate antigen-specific CD4 + and CD8 + T cells. This suggests that NV pseudotyped LVs might possibly be more immunogenic than first thought.…”