Recombinant Vaccine

Sep 20, 2021

Summary

The COVID-19 pandemic has caused 4.51 million deaths so far (Wikipeida, 2021). Even though mass vaccinations have been ongoing for a couple of months to fight the native agent of the disease, some highly transmissible variants driving an uptick in COVID-19 cases may have evaded current vaccine-elicited antibodies. Recently, a newly developed mRNA vaccine (mRNA-1273.351) and a novel circular RNA vaccine (circRNA^RBD) have shown potent neutralizing ability for different variants of concern, bringing new hopes for stopping the pandemic (Wu et al. 2021b; Qu et al. 2021).

Background

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attracts constant attention as the toll of deaths and infections is still growing around the world. Several vaccines are now available for human use, including the first approved RNA vaccine (mRNA-1273) with as high as 94% efficacy against COVID-19. Nevertheless, various SARS-CoV-2 variants are emerging and spreading worldwide, rising concerns of viral escape from immunity prompted by current vaccinations. In order to meet the urgent demand for more vaccines inducing broad and potent neutralization of variants of concern, researchers are trying to develop new vaccines based on different types of RNA, such as mRNA and circular RNA. mRNA-1273.351 is an optimized vaccine based on mRNA-1273 while circRNA^RBD vaccine is a novel type of vaccine based on nanotechnology.

Experiment

The Design and Evaluation of a New mRNA Vaccine

Wu et al. produced mRNAs (mRNA-1273.351) encoding spike protein of native SARS-CoV-2 or B.1.351 variant and encapsulated them in a novel lipid nanoparticle. The Recombinant Protein corresponding to the spike protein of native SARS-CoV-2 was provided by GenScript.
In a two-dose scenario, experimental mice were injected twice with mRNA-1273.351 at a three-week interval, and the neutralizing antibody titers were assessed 2 weeks after the first and

The Design and Evaluation of circRNA Vaccine

Qu et al. synthesized circular RNA encoding SARS-CoV-2 RBD antigens and encapsulated it within lipid nanoparticles. The complex was termed LNP-circRNA^RBD, which was injected intramuscularly into mice twice on a 0,14-day schedule and assessed 2 and 5 weeks after the second dose. They also design a cirRNA vaccine encoding RBD derived from B.1.351 variant (circRNA^RBD-501Y.V2) and evaluate the neutralization activity of mouse serum samples against various circulating variants, including D614G, B.1.1.7, and B.1.351. GenScript offered SARS-CoV-2 Surrogate Virus Neutralization Test Kit to detect the neutralizing activity of mice sera in this study.

Results

The researchers observed higher neutralization titers in mice 2 weeks after the second dose of the mRNA vaccine (mRNA-1273.351) than those previously reported with mRNA-1273 (Wu et al. 2021a), which has been approved for emergency use since December 2020, indicating that the novel mRNA vaccine could provide better protection against the B.1.351 variant. Moreover, data also revealed that the third dose of mRNA-1273.351 could significantly increase the level of antibody binding in assays using B.1.351 and D614G variants.

On the other hand, Qu et al. found that the circRNA^RBD vaccine could induce high titers of RBD-specific IgG and elicit evident neutralizing antibodies. Further experiments revealed that the circRNA^RBD-501Y.V2 vaccine-induced antibodies effectively neutralized all viral strains. Additionally, researchers showed that anti-SARS-CoV2 nanobodies encoded by circRNAs could be developed as a treatment option for COVID-19 patients. Their ability to neutralize SARS-CoV-2 was demonstrated through in vitro pseudovirus assays.

In summary, both the novel mRNA vaccine and the circRNA vaccine have preferential neutralizing abilities to the corresponding SARS-CoV-2 variants and hold potentials in preventing the escape of emerging variants from vaccine-elicited protective immunity.

Reference

• Qu, Liang, et al. "Circular RNA vaccines against SARS-CoV-2 and emerging variants." bioRxiv (2021).
• Wikipedia, “COVID-19 pandemic data” Wikipedia (2021).
• Wu, Kai, et al. "Serum neutralizing activity elicited by mRNA-1273 vaccine." New England Journal of Medicine 384.15 (2021a): 1468-1470.
• Wu, Kai, et al. "Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice." bioRxiv (2021b).

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