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A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus.

ABSTRACT: Sendai virus fresh isolates were shown to be antigenically different from the prototype Fushimi strain that had long been passaged in embryonated chicken eggs. Phylogenetic analysis of the hemagglutinin-neuraminidase genes also revealed the difference between these two virus groups. Both trypsin-resistant and elastase-sensitive mutations were additionally introduced to an LLC-MK2-cell-adapted and attenuated mutant derived from one of the fresh isolates. This protease activation mutant (MVCES1) showed the same antigenicity as the fresh isolates, and as a result of a single cycle of growth in lungs, it could confer better protection on mice against challenge infection with the currently prevailing Sendai virus than TR-5, which is a trypsin-resistant mutant derived from the Fushimi strain. The eligibility of MVCES1 as an attenuated live vaccine of Sendai virus is discussed.

SUBMITTER: Wang XL

PROVIDER: S-EPMC236828 | biostudies-other | 1994 May

REPOSITORIES: biostudies-other

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A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus.

Wang X L XL Itoh M M Hotta H H Homma M M

Journal of virology 19940501 5

Sendai virus fresh isolates were shown to be antigenically different from the prototype Fushimi strain that had long been passaged in embryonated chicken eggs. Phylogenetic analysis of the hemagglutinin-neuraminidase genes also revealed the difference between these two virus groups. Both trypsin-resistant and elastase-sensitive mutations were additionally introduced to an LLC-MK2-cell-adapted and attenuated mutant derived from one of the fresh isolates. This protease activation mutant (MVCES1) s ...[more]

PMID: 8151795

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Project description:Newcastle disease virus (NDV) can cause severe disease in chickens. Although NDV vaccines exist, there are frequent reports of outbreaks in vaccinated chickens. During 2009-2010, despite intense vaccination, NDV caused major outbreaks among commercial poultry farms in Indonesia. These outbreaks raised concern regarding the protective immunity of current vaccines against circulating virulent strains in Indonesia. In this study, we investigated whether a recombinant attenuated Indonesian NDV strain could provide better protection against prevalent Indonesian viruses. A reverse genetics system for the highly virulent NDV strain Banjarmasin/010/10 (Ban/010) isolated in Indonesia in 2010 was constructed. The Ban/010 virus is classified in genotype VII of class II NDV, which is genetically distinct from the commercial vaccine strains B1 and LaSota, which belong to genotype II, and shares only 89 and 87% amino acid identity for the protective antigens F and HN, respectively. A mutant virus, named Ban/AF, was developed in which the virulent F protein cleavage site motif "RRQKR↓F" was modified to an avirulent motif "GRQGR↓L" by three amino acid substitutions (underlined). The Ban/AF vaccine virus did not produce syncytia or plaques in cell culture, even in the presence of added protease. Pathogenicity tests showed that Ban/AF was completely avirulent. Ban/AF replicated efficiently during 10 consecutive passages in chickens and remained genetically stable. Serological analysis showed that Ban/AF induced higher neutralization and hemagglutination inhibition antibody titers against the prevalent viruses than the commercial vaccines B1 or LaSota. Both Ban/AF and commercial vaccines provided protection against clinical disease and mortality after challenge with virulent NDV strain Ban/010 (genotype VII) or GB Texas (genotype II). However, Ban/AF significantly reduced challenge virus shedding from the vaccinated birds compared to B1 vaccine. These results suggest that Ban/AF can provide better protection than commercial vaccines and is a promising vaccine candidate against NDV strains circulating in Indonesia.

Dataset Information

A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus.

Publications

A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus.

Similar Datasets

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