A Yellow Fever 17D Virus Replicon-Based Vaccine Platform for Emerging Coronaviruses

Vaccines

Tim J. Dalebout¹  Irina C. Albulescu¹  Sebenzile K. Myeni¹  Nadia Oreshkova¹  Peter J. Bredenbeek¹  Eric J. Snijder¹  Marjolein Kikkert¹  Niraj Mishra²  Kai Dallmeier² 

[1] Center of Infectious Diseases LU-CID, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49 Box 1043, 3000 Leuven, Belgium;

关键词: coronavirus;    vaccine platform;    YFV-17D;    YF17D;    MERS-CoV;    SARS-CoV;   

DOI  :  10.3390/vaccines9121492

来源: DOAJ

【 摘 要 】

The tremendous global impact of the current SARS-CoV-2 pandemic, as well as other current and recent outbreaks of (re)emerging viruses, emphasize the need for fast-track development of effective vaccines. Yellow fever virus 17D (YF17D) is a live-attenuated virus vaccine with an impressive efficacy record in humans, and therefore, it is a very attractive platform for the development of novel chimeric vaccines against various pathogens. In the present study, we generated a YF17D-based replicon vaccine platform by replacing the prM and E surface proteins of YF17D with antigenic subdomains from the spike (S) proteins of three different betacoronaviruses: MERS-CoV, SARS-CoV and MHV. The prM and E proteins were provided in trans for the packaging of these RNA replicons into single-round infectious particles capable of expressing coronavirus antigens in infected cells. YF17D replicon particles expressing the S1 regions of the MERS-CoV and SARS-CoV spike proteins were immunogenic in mice and elicited (neutralizing) antibody responses against both the YF17D vector and the coronavirus inserts. Thus, YF17D replicon-based vaccines, and their potential DNA- or mRNA-based derivatives, may constitute a promising and particularly safe vaccine platform for current and future emerging coronaviruses.

【 授权许可】

Unknown