Chimney vaccines can provide universal protection against viruses such as SARS-CoV-2

Researchers in the United States have developed “chimney” vaccines that provide cross-protection against various strains of sarbecovirus in mice, including the novel respiratory bad syndrome coronavirus 2 (SARS-CoV-2 ) causing 2019 coronavirus infection (COVID-19).

Sarbecoviruses are the subgenus of group II coronaviruses or betacoronaviruses that are one of the four genes (alpha, beta, gamma, and delta) that make up coronaviruses.

The researchers say that three outbreaks of sarbecovirus outbreaks (SARS-CoV-1, SARS-CoV-2, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV) have appeared in just the last two decades of clarify the need for universal vaccination strategies against SARS.

The Moderna and Pfizer-BioNTech vaccines containing RNA encoding (mRNA) for SARS-CoV-2 spike proteins have been shown to be effective in protecting against COVID-19 in phase 3 trials. This spike is the main surface structure used by the virus to infest cells and the main target is to neutralize antibodies following a natural infection or vaccine.

However, studies have shown that some recently revealed variants, such as the South African B1.351 line, are more resistant to vaccine-neutralizing antibodies. This has led to growing concerns that stronger approaches are needed to prevent future zandotic coronavirus infections similar to SARS.

Now, David Martinez of the University of North Carolina at Chapel Hill and colleagues have shown that chimney spike designs based on epidemic and pandemic sarbecoviruses protected aged mice against infection with three high-risk betacoronaviruses and B.1.351 SARS-CoV- South Africa. 2 various concerns.

“Thus, complex chimney spikes may provide a new strategy to prevent zandotic coronavirus-like infections,” the team writes.

A pre-printed version of the research paper can be found on the bioRxiv* server, while the article is subject to peer review.

Three pathogenic sarbecovirus outbreaks in the last 20 years

Following the outbreak of the SARS-CoV-1 virus in 2003, which caused more than 800 deaths worldwide, MERS-CoV emerged within less than a decade, leading to a sustained uprising that caused at least 900 deaths.

In December 2019, when another novel sarbecovirus appeared in Wuhan, China – SARS-CoV-2 –quickly came a global pandemic that has now caused more than 120 million infections and more than 2.65 million deaths.

“Because of the high pandemic potential of zoonotic (animal-to-human) and epidemic sarbecoviruses, the development of general approaches such as universal vaccination strategies, antibodies and drugs is a global health priority,” says Martinez and his colleagues. jobs.

The challenges facing vaccine development

However, a key challenge is the development of vaccines that can neutralize diverse sarbecoviruses of the broad genetic diversity of critical immune epitope forms such as the receptor binding domain (RBD) of the spike protein .

Studies have shown that plasma from patients who have undergone COVID-19 shows little over-neutralization of other human pathogenic coronaviruses such as SARS-CoV and MERS-CoV.

Researchers are therefore unsure whether immunization after natural infection or vaccination will provide protection against sarbecoviruses of zoonotic origin that may occur in the future.

In addition to the RBD of the spike protein, N-terminal domain (NTD) is also a target to neutralize antibodies against SARS-CoV-2 and MERS-CoV.

Building on the rapid development and success of the Moderna and Pfizer-BioNTech nanoparticle vaccine platforms in large-scale phase 3 clinical trials, Martinez and colleagues replicated the existing platform to test whether chimney spikes containing a combination of the RBD and NTD from various epidemic and pandemic sarbecoviruses were protected against the viruses in older mouse models.

What did they find?

The team found that chimney spike mRNA containing both NTD and RBD contained high levels of neutral neutral antibodies against three high-risk sarbecoviruses, namely SARS-CoV and bat-like coronaviruses similar to SARS RsSHC014 and WIV1WIV-1.

In contrast, mice vaccinated with monovalent SARS-CoV-2 mRNA vaccine showed up to more than 500-fold reduction in neutralizing antibody activity against different sarbecovirus strains.

In addition, SARS-CoV infection in these mice caused rupture infections, including measurable lung disease.

The findings highlight the need for universal vaccination strategies

“The lack of protection against SARS-CoV challenge in SARS-CoV-2 vaccinated mice reinforces the need to develop universal vaccination strategies that will provide wider coverage against SARS-CoV-predisposed bats- and SARS-CoV-2 – similar to viruses, ”the team wrote.

Importantly, the chimney spike mRNA vaccines also effectively neutralized both D614G and South African B.1.351 SARS-CoV-2 anxiety modifications.

“Our findings suggest that mRNA-LNP vaccination with chimney coronavirus spikes is an operational strategy to protect against contemporary and high-risk sarbecovirus emergencies,” said Martinez and colleagues.

“Our demonstration of over-protection against sarbecoviruses in mice supports the notion that universal vaccines against group 2B coronaviruses appear to be possible,” they conclude.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.