bioRxiv: mRNA vaccine 2.0!

In early 2020, the pneumonia epidemic caused by the new coronavirus (SARS-CoV-2) began to become a global pandemic and has continued to this day

World Health Organization (WHO) World Health Organization (WHO) Over 320 million people infected Over 320 million people infected Over 5.

This reminds us that in the context of the constant mutation of the new coronavirus, the effectiveness of existing vaccines and therapeutic antibodies has begun to gradually decline

On January 11, 2022, the team of Wei Wensheng of Peking University published on the preprint platform bioRxiv entitled: Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants (circular RNA vaccine against SARS-CoV-2 and new variants ) research paper

bioRxiv bioRxiv Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants New variant of circular RNA vaccine)

On the basis of the bioRxiv paper published in March last year, Wei Wensheng's team validated their previously developed circular RNA vaccine (circRNA-RBD) encoding the new coronavirus spike protein trimer receptor binding domain (RBD) in rhesus monkeys.

Different from the linear mRNA vaccines currently used, this circular RNA vaccine, because the circular RNA itself has high stability , does not require nucleotide modification, and can be stored at room temperature for 2 weeks without affecting the effect .

Very high stability, high stability, storage for 2 weeks , storage for 2 weeks , no effect , no effect , circular RNA vaccine has very good application prospects in the fight against new coronavirus variant virus.

Vaccination is the most promising way to end and prevent the Covid-19 pandemic

mRNA vaccines have the advantages of fast production speed , low cost , and rapid response to virus mutation

Fast production speed Fast production speed Low cost and low cost Fast response to virus mutation Fast response to virus mutation Immunogenic side effects Immunogenic side effects

In nature, circular RNAs (circRNAs) are ubiquitous in fungi, plants, insects, fish, and mammals, and even the genomes of some viruses themselves are circular RNAs, such as hepatitis D virus and plant viroids

So far, only a few endogenous circular RNAs have been shown to serve as templates for protein translation

Wei Wensheng's team designed a circular RNA vaccine for the new coronavirus and its variants.

The research team used self-splicing type I intron ribozymes to generate circular RNAs - circRNA-RBDs - encoding SARS-CoV-2-RBD antigens

Schematic diagram of the design of circRNA-RBD

Design pattern of circRNA-RBD Design pattern of circRNA-RBD

Cell experiments show that circRNA-RBD can express the RBD antigen of 2019-nCoV in human cells and mouse cells, and the expression level is significantly higher than that of linear mRNA-RBD, and it can effectively block the infection of cells by 2019-nCoV pseudovirus

In mouse experiments, circRNA-RBD delivered by lipid nanoparticles (LNP) could effectively neutralize the new coronavirus pseudovirus, and a strong T cell immune response was generated in the spleen of mice

circRNA-RBD vaccine induces durable humoral immune responses and strong T-cell immune responses in mice

circRNA-RBD vaccine induces durable humoral immune response and strong T cell immune response in mice circRNA-RBD vaccine induces durable humoral immune response and strong T cell immune response in mice

The research team also designed a circRNA-RBD vaccine against the Delta mutant strain, and the experimental results showed that the vaccine could produce high levels of neutralizing antibodies against the Delta and Omicron mutant strains

This time, the research team also tested the effect of the circular RNA vaccine in monkeys, and the experimental results showed that the circular RNA vaccine can effectively protect rhesus monkeys
.

Lipid nanoparticle (LNP)-delivered circular RNA vaccines elicit potent neutralizing antibody and T-cell responses, producing stronger and longer-lasting effects than modified linear mRNA vaccines
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Importantly, the study found that a circular RNA vaccine against Omicron could only induce high levels of neutralizing antibodies against Omicron, while a circular RNA vaccine against Delta could induce both high levels of neutralizing antibodies against Delta and high levels of neutralizing antibodies against Delta.
High-level neutralizing antibodies against Omicron
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This suggests that the circular RNA vaccine against Delta is a powerful vaccine option that could provide broad protection against the current major strains of COVID-19
.

Overall, this study confirms that circular RNA vaccines have the advantages of good thermal stability, high expression of encoded antigens, and wide applicability, and the corresponding circular RNA vaccines have been successfully designed to fight 2019-nCoV and its mutants infection, suggesting that circular RNA vaccines could serve as a novel vaccine and therapeutic platform in the COVID-19 pandemic
.

Original source:

Liang Qu, Zongyi Yi, Yong Shen, et al.
Circular RNA Vaccine against SARS-CoV-2 and Emerging Variants .
bioRxiv, 2022.

Circular RNA Vaccine against SARS-CoV-2 and Emerging Variants

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