Journal
VIRUSES-BASEL
Volume 10, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/v10050234
Keywords
HSV-1; mutant strain; immunogenicity; rhesus macaques
Categories
Funding
- PUMC Youth Fund of the Fundamental Research Funds for the Central Universities [3332016115]
- CAMS Initiative for Innovative Medicine [2016-I2M-1-019]
- National Natural Science Foundation of China [31670173]
- Natural Science Foundation of Yunnan Province [2014FB191]
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Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.
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