title: Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.
abstract: Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan. yone@ims.u-tokyo.ac.jp
authors.forename: Misako
authors.initials: M
authors.lastname: Yoneda
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Georges-Courbot
authors.forename: Fusako
authors.initials: F
authors.lastname: Ikeda
authors.forename: Miho
authors.initials: M
authors.lastname: Ishii
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Frederic
authors.initials: F
authors.lastname: Jacquot
authors.forename: Hervé
authors.initials: H
authors.lastname: Raoul
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001831:Body Temperature; D001835:Body Weight; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D045464:Henipavirus Infections / Q000401:mortality / Q000517:prevention & control*; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008459:Measles virus / Q000235:genetics*; D045405:Nipah Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines