Search

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. [ABSTRACT FROM AUTHOR]

In previous studies oncolytic measles viruses (MVs) have shown significant antitumor activity against various tumors. In our research recombinant MV-Hu191 (rMV-Hu191), established via reverse genetics technology and expressing enhanced green fluorescent protein (EGFP), was evaluated for its therapeutic effects and related mechanisms against nephroblastoma cell lines. We built three different constructs based on rMV-Hu191 to express EGFP effectively. Our experiments showed that rMV-Hu191 expressing EGFP could efficiently infect and replicate in nephroblastoma cell lines. Caspase-induced apoptosis exerted a significant impact on MV-induced cell death, which was accompanied by emission of cellular ATP and high-mobility group protein 1 (HMGB1) and by translocation of calreticulin (CRT). Intratumoral injection of rMV-Hu191-EGFP resulted in significant regression of tumors in a G401 xenograft model. Our results indicate that the MV-Hu191 strain, which is widely used in China, is an appropriate vector for expression of foreign genes and could serve as a potentially good candidate for nephroblastoma therapy mediated by induction of apoptosis-associated immunogenic cell death (ICD)., Competing Interests: None., (AJTR Copyright © 2021.)