1. Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein.
- Author
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Wang Y, Liu R, Lu M, Yang Y, Zhou D, Hao X, Zhou D, Wang B, Li J, Huang YW, and Zhao Z
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Binding Sites, China, Chlorocebus aethiops, Female, Humans, Measles Vaccine administration & dosage, Measles Vaccine genetics, Measles virus immunology, Protein Binding, Reverse Genetics, Sigmodontinae, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated adverse effects, Vaccines, Attenuated genetics, Vaccines, Attenuated immunology, Vero Cells, Measles Vaccine adverse effects, Measles Vaccine immunology, Measles virus pathogenicity, Mutation, RNA-Dependent RNA Polymerase genetics, RNA-Dependent RNA Polymerase metabolism, S-Adenosylmethionine metabolism
- Abstract
The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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