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Novel mRNA vaccines encoding Monkeypox virus proteins show promise in preclinical studies

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In a recent study posted on Bio Rxiv*Preprint Server, Chinese researchers demonstrate the efficacy of a three messenger ribonucleic acid (mRNA) technology-based monkeypox virus (MPXV) vaccine in combating a lethal vaccinia virus (VACV) challenge in a mouse model. Proven.

study: Novel mRNA vaccines encoding monkeypox viruses M1R and A35R protect mice against lethal viral challengeImage credit: NIAID

Background

MPXV belongs to the Poxviridae family, which also has variola virus (smallpox) and VACV. In the 1980s, live viral preparations of infectious vaccinia virus eradicated smallpox worldwide. Like all his MPXV vaccines licensed, the replication-attenuated live virus vaccine expresses many viral proteins, which raises safety concerns.

Extracellular enveloped virus (EEV) and intracellular mature virus (IMV) are two infectious forms of MPXV. However, subunit vaccines using these have shown superior safety profiles to live virus vaccines in small animal models. For example, Lai et al. We showed that vaccination with E. coli expressing A27L, a truncated IMV surface protein, protected mice from lethal VACV challenge. Therefore, more MPXV antigens and better vaccine combination strategies against MPXV should be explored.

Moreover, since MPXV was declared a public health emergency by the World Health Organization (WHO) in July 2022, there is a further need for a more effective MPXV vaccine. mRNA vaccine technology is used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), all vaccines are based on mRNA technology and show high efficacy and safety.

About research

Inspired by the success of mRNA vaccines against SARS-CoV-2, researchers in this study developed three mRNA vaccines against MPXV, VGPox1, VGPox2, and VGPox3. These vaccines expressed the MPXV EEV protein A35R and the IMV protein M1R, homologues of his VACV A33R and L1R, respectively. VGPox 1 and 2 were single mRNA molecules encoding fusion proteins composed of A35R EEV and full-length M1R, whereas VGPox 3 was an mRNA-lipid nanoparticle (LNP) complex encoding A35R and M1R, respectively. was a mixture of The only difference between VGPox 1 and 2 was the absence of the A35R stalk region in the latter.

The researchers tested these three vaccines for humoral and cellular anti-VACV immunity and their protection against lethal viral infection in mice. The team inoculated each mouse intranasally with 1×10.6 Plaque-forming unit (PFU) VACV-WR virus 36 days after vaccination.

They were weighed and monitored for symptoms daily until sacrifice. Animals were sacrificed on day 9 after virus challenge or when their body weight had decreased by more than 15% of hers. They took the animal’s lungs, pulverized them with a tissue homogenizer, and then freeze-thawed them three times to release the virus from the cells. Then, different dilutions of supernatant were added to VeroE6 cells for plaque assay.

Survey results

The study results showed that all three mRNA vaccines induced similar levels of anti-A35R antibodies, but only VGPox 1 and 2 induced higher antibody levels against M1R. Vaccinated sera from chives were able to neutralize live virus at early time points.As expected, the VGPox 3 vaccine was ineffective in vitro Neutralization assay. Interestingly, VGPox2 showed higher levels of total immunoglobulin G (IgG) to his M1R than VGPox1 and VGPox3 at all time points. Also, VGPox1 showed lower protein expression levels than VGPox2 in T cells. However, researchers were unable to determine how differences in protein expression levels contributed to his IgG levels induced by the two vaccines.

Conclusion

An mRNA vaccine encoding fusions of A35R and M1R (VGPox 1 and VGPox 2) effectively induced high levels of both A35R and M1R IgG and neutralized live virus in cell culture at all time points. did. However, a mixture of these two mRNAs (VGPox 3) failed to achieve the same results as M1R-specific antibodies induced by VGPox 3 much later. Nonetheless, all three mRNA vaccines tested in this study conferred 100% protection during virus challenge assays. Presumably, when all test animals were challenged with live virus on his 36th day, both anti-A35R and anti-M1R neutralizing antibodies were induced by all three of her vaccines.

Neutralizing antibodies to EEV and IMV may confer protection against live virus attack. Thus, despite the slow induction of anti-M1R antibodies, it remains unclear how VGPox3 protected mice during lethal viral challenge. In conclusion, given the high homology between vaccinia and MPXV, both VGPox 1 and 2 could be potent mRNA vaccines against MPXV, as they fully protected mice during lethal vaccinia virus challenge. there is.

*Important Notices

Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

Journal reference:

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