| Title: |
Development of a Novel, Single-Cycle Replicable Rift Valley Fever Vaccine. |
| Authors: |
Murakami, Shin1 (AUTHOR), Terasaki, Kaori1 (AUTHOR), Ramirez, Sydney I.2 (AUTHOR), Morrill, John C.1 (AUTHOR), Makino, Shinji1,3,4,5 (AUTHOR) shmakino@utmb.edu |
| Source: |
PLoS Neglected Tropical Diseases. 3/20/2014, Vol. 8 Issue 3, p1-13. 13p. |
| Subject Terms: |
*RIFT Valley fever, *NEUTRALIZATION tests, *GREEN fluorescent protein, *VIRAL envelope proteins, *AMPLIFICATION reactions, *VIRUS-like particles, *IMMUNIZATION of children, *ALPHAVIRUSES, *VIRAL encephalitis |
| Abstract: |
Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, neuroinvasiveness and neurovirulence of MP-12 in mice may be a concern when vaccinating certain individuals, especially those that are immunocompromised. We have developed a novel, single-cycle replicable MP-12 (scMP-12), which carries an L RNA, M RNA mutant encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function, and S RNA encoding N protein and green fluorescent protein. The scMP-12 underwent efficient amplification, then formed plaques and retained the introduced mutation after serial passages in a cell line stably expressing viral envelope proteins. However, inoculation of the scMP-12 into naïve cells resulted in a single round of viral replication, and production of low levels of noninfectious virus-like particles. Intracranial inoculation of scMP-12 into suckling mice did not cause clinical signs or death, a finding which demonstrated that the scMP-12 lacked neurovirulence. Mice immunized with a single dose of scMP-12 produced neutralizing antibodies, whose titers were higher than in mice immunized with replicon particles carrying L RNA and S RNA encoding N protein and green fluorescent protein. Moreover, 90% of the scMP-12-immunized mice were protected from wild-type RVFV challenge by efficiently suppressing viremia and replication of the challenge virus in the liver and the spleen. These data demonstrated that scMP-12 is a safe and immunogenic RVFV vaccine candidate. Author Summary: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen, which causes febrile illness, encephalitis and fatal hemorrhagic fever in humans and severe hepatic disease with high mortality and spontaneous abortion rates in ruminants. RVFV is endemic to the African continent. Because many different mosquito species support RVFV replication, the virus has the potential to spread to other areas of the world, such as North and South America, Asia, and Europe and could cause serious public health problems and economic losses. Consistent with this concern, RVFV has caused epidemic disease in the Arabian Peninsula. Currently, there is no approved vaccine suitable for mass vaccination programs of humans. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, its neuroinvasiveness and neurovirulence in mice are areas of concern, especially when considering the immunization of children and the immunocompromised. In this study, we present a novel MP-12-based, single-cycle replicable RVF vaccine candidate. This vaccine candidate was not neurovirulent in mice and was effective in protecting immunized mice from wild-type RVFV challenge, indicating its potential to be developed as a safe vaccine for use in both humans and livestock. [ABSTRACT FROM AUTHOR] |
|
Copyright of PLoS Neglected Tropical Diseases is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
