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Novel avian paramyxovirus-based vaccine vectors expressing the Ebola virus glycoprotein elicit mucosal and humoral immune responses in guinea pigs.

ABSTRACT: Paramyxovirus vaccine vectors based on human parainfluenza virus type 3 (HPIV-3) and Newcastle disease virus (NDV) have been previously evaluated against Ebola virus (EBOV) challenge. Although both the viral vectored vaccines efficiently induce protective immunity, some concerns remain to be solved. Since HPIV-3 is a common human pathogen, the human population has pre-existing immunity to HPIV-3, which may restrict the replication of the vaccine vector. For NDV, mesogenic (intermediate virulent) strain used in previous studies is currently classified as a Select Agent in the United States, thus making it unsuitable to be used as a vaccine vector. To overcome these concerns, we have developed a modified NDV vector based on a mesogenic NDV strain, in which the ectodomains of envelope glycoproteins were replaced with the corresponding ectodomains from avian paramyxovirus serotype 3 (APMV-3). The modified NDV vector was highly attenuated in chickens and was able to express the EBOV glycoprotein (GP) gene at high level. In addition, the recombinant APMV-3 was also evaluated as a vaccine vector to express the EBOV GP gene. Guinea pigs immunized with these two vector vaccines developed high levels of neutralizing GP-specific IgG and IgA antibodies.

SUBMITTER: Yoshida A

PROVIDER: S-EPMC6445115 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Novel avian paramyxovirus-based vaccine vectors expressing the Ebola virus glycoprotein elicit mucosal and humoral immune responses in guinea pigs.

Yoshida Asuka A Kim Shin-Hee SH Manoharan Vinoth K VK Varghese Berin P BP Paldurai Anandan A Samal Siba K SK

Scientific reports 20190402 1

Paramyxovirus vaccine vectors based on human parainfluenza virus type 3 (HPIV-3) and Newcastle disease virus (NDV) have been previously evaluated against Ebola virus (EBOV) challenge. Although both the viral vectored vaccines efficiently induce protective immunity, some concerns remain to be solved. Since HPIV-3 is a common human pathogen, the human population has pre-existing immunity to HPIV-3, which may restrict the replication of the vaccine vector. For NDV, mesogenic (intermediate virulent) ...[more]

PMID: 30940854

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Project description:UnlabelledEbola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals. The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances.ImportanceEbola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread from pigs to monkeys without direct contact. Further studies have been hampered, because an economical animal model for Ebola transmission is not available. To address this, we established a transmission model in guinea pigs and determined the mechanisms behind virus spread. The survival data, in addition to microscopic examination of lung and trachea sections, show that mucosal infection of guinea pigs is an efficient model for Ebola transmission. Virus spread is increased with longer contact times with an infected animal and is possible without direct contact between an infected and a naive host but can be stopped if infectious materials are absent. These results warrant consideration for the development of future strategies against Ebola transmission and for a better understanding of the parameters involved in virus spread.

Dataset Information

Novel avian paramyxovirus-based vaccine vectors expressing the Ebola virus glycoprotein elicit mucosal and humoral immune responses in guinea pigs.

Publications

Novel avian paramyxovirus-based vaccine vectors expressing the Ebola virus glycoprotein elicit mucosal and humoral immune responses in guinea pigs.

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