Abstract
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.
Highlights
In the last two decades, theemergence of a series of RNA virus pathogens led to serious disease outbreaks in humans
For the generation of a Yellow fever virus 17D (YF17D)-replicon vaccine platform, the viral gene sequences encoding the prM and E genes of yellow fever virus (YFV) were replaced with a gene sequence encoding a foreign viral protein of interest (Figure 1A,B)
For preservation of the membrane topology, it is pertinent that in the natural YFV polyprotein, the sequence encoding the transmembrane anchor (TMA) of the capsid protein serves as a signal sequence for the prM protein, while the TMA of the E protein serves as a signal sequence for the NS1 protein (Figure 1C, left panel)
Summary
In the last two decades, the (re)emergence of a series of RNA virus pathogens led to serious disease outbreaks in humans. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in Saudi Arabia; this virus, to date, continues to cause a relatively small number of infections, mostly by direct transmission from dromedary camels and subsequent spread in household or hospital care settings. Other recent epidemics, such as those caused by the Ebola and Zika viruses, are not new to humans, but are causing recurrent outbreaks or spreading to new territories. This recent epidemic and pandemic history, as well as the current pandemic situation, underscore the need for adequate preparedness and fast and efficient production of remedies against (re)emerging infectious diseases
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