Immunogenicity and Therapeutic Efficacy of a Sendai-Virus-Vectored HSV-2 Vaccine in Mouse and Guinea Pig Models

仙台病毒载体 HSV-2 疫苗在小鼠和豚鼠模型中的免疫原性和治疗效果

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作者:Xiuxiu Ren, Wenhao Su, Shishi Li, Tingting Zhao, Qiufang Huang, Yinan Wang, Xiaojie Wang, Xiaohuan Zhang, Jiangbo Wei

Background

To date, there is no licensed vaccine for preventing herpes simplex virus type 2 (HSV-2). The current treatment to address the infection and prevent its transmission is not always satisfactory.

Conclusions

The replication-defective recombinant Sendai viruses conveying HSV-2-gD and ICP27 proteins showed great immunogenicity and potential for preventing recurrent HSV-2 disease.

Methods

We constructed two recombinant vectors, one encoding HSV-2 glycoprotein D (gD, SeV-dF/HSV-2-gD) and one encoding HSV-2-infected cell protein 27 (ICP27, SeV-dF/HSV-2-ICP27), based on a replication-defective Sendai virus through reverse genetics, collectively comprising a combinatorial HSV-2 therapeutic vaccine candidate. The immunogenicity and proper immunization procedure for this vaccine were explored in a murine model. The therapeutic effect that helps prevent recurrent HSV-2 disease was evaluated in HSV-2-infected guinea pigs.

Results

Both a robust humoral immune response and a cellular immune response, characterized by the neutralizing antibody titer and the IFN-γ level, respectively, were elicited in BALB/c mice. A further study of cellular immunogenicity in mice revealed that T lymphocytes were successfully enhanced with the desirable secretion of several cytokines. In HSV-2-seropositive guinea pigs, vaccination could reduce the severity of HSV-2 in terms of recurrent lesions, duration of recurrent outbreak, and frequency of recurrence by 58.66%, 45.34%, and 45.09%, respectively, while viral shedding was also significantly inhibited in the vaccine-treated group compared to the group treated with phosphate-buffered saline. Conclusions: The replication-defective recombinant Sendai viruses conveying HSV-2-gD and ICP27 proteins showed great immunogenicity and potential for preventing recurrent HSV-2 disease.

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