In addition to the RBD of the spike protein, the N-terminal domain (NTD) is also a target of neutralizing antibodies against SARS-CoV-2 and MERS-CoV. Researchers are, therefore, uncertain whether immunity following natural infection or vaccination will protect against sarbecoviruses of zoonotic origin that may emerge in the future. Studies have shown that plasma from patients who have recovered from COVID-19 exhibit little cross-neutralization of other human pathogenic coronaviruses such as SARS-CoV and MERS-CoV. However, a major challenge faced in developing vaccines that can neutralize diverse sarbecoviruses is the broad genetic diversity that exists within critical immunodominant epitope landscapes such as the receptor-binding domain (RBD) of the spike protein. The challenges faced in vaccine development “Given the high pandemic potential of zoonotic (animal-to-human) and epidemic sarbecoviruses, the development of broadly effective approaches such as universal vaccination strategies, antibodies and drugs is a global health priority,” says Martinez and colleagues. In December 2019, the emergence of another novel sarbecovirus in Wuhan, China – SARS-CoV-2 –quickly led to a global pandemic that has now caused more than 120 million infections and more than 2.65 million deaths. The SARS-CoV-1 virus that emerged in 2003 and caused more than 800 deaths worldwide was followed by the emergence of MERS-CoV within less than a decade, which resulted in an ongoing outbreak that caused at least 900 deaths. Three pathogenic sarbecovirus outbreaks in the last 20 years (H) Nanoluciferase expression of RsSHC014/SARS CoV-2 chimeric spike live viruses. Protein expression of chimeric spikes, SARS-CoV-2 furin KO, and norovirus mRNA vaccines. (E) SARS-CoV-2 furin KO spike vaccine and (F) is the norovirus capsid vaccine. (D) Spike chimera 4 includes the RBD from RsSHC014 and the rest of the spike from SARS CoV-2. (C) Spike chimera 3 includes the RBD from SARS-CoV and the NTD and S2 SARS-CoV 2. (B) Spike chimera 2 includes the RBD from SARS-CoV-2 and the NTD and S2 from SARS CoV. (A) Spike chimera 1 includes the NTD from HKU3-1, the RBD from SARS-CoV, and the rest of the spike from SARS-CoV-2.
“Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections,” writes the team.Ī pre-print version of the research paper is available on the bioRxiv * server, while the article undergoes peer review.Ĭhimeric spike constructs from sarbecoviruses. Now, David Martinez from the University of North Carolina at Chapel Hill and colleagues have shown that chimeric spike designs based on different epidemic and pandemic sarbecoviruses protected aged mice against infection with three high-risk betacoronaviruses and the South African B.1.351 SARS-CoV-2 variant of concern. This has led to growing concerns that more robust approaches are needed to prevent the pandemic and SARS-like zoonotic coronavirus infections in the future. However, studies have shown that some recently emerged variants of concern, such as the South African B1.351 lineage, are more resistant to vaccine-elicited neutralizing antibodies. This spike protein is the main surface structure the virus uses to infect cells and the primary target of neutralizing antibodies following natural infection or vaccination. The Moderna and Pfizer-BioNTech vaccines that contain messenger RNA (mRNA) coding for the SARS-CoV-2 spike protein proved effective at protecting against COVID-19 in phase 3 trials. The researchers say the emergence of three sarbecovirus outbreaks (SARS-CoV-1, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV) in just the last two decades highlights the need for universal vaccination strategies against SARS-related sarbecoviruses. Sarbecoviruses are the subgenus of group II coronaviruses or betacoronaviruses that is one of the four genera (alpha, beta, gamma, and delta) that make up coronaviruses. Study: Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice.
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