A potential mRNA vaccine for SARS-CoV-2 Omicron variant


Since the emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) in November 2021, it has become the dominant variant of concern in most countries, accounting for 99% of new infections. This is due to Omicrons high transmissibility.

Because of its 30 mutations, the Omicron variant is able to escape the majority of existing SARS-CoV-2 neutralizing antibodies (nAbs). This has led to the inability of the spike (S) protein monoclonal antibodies to neutralise Omicron. Individuals who have been previously been infected with other SARS-CoV-2 variants were reported to have minimal nAbs against Omicron, making them susceptible to reinfection.

It has been reported that a third dose or booster of available common COVID-19 vaccines is an effective measure for reducing deaths, hospitalisations, and severe disease caused by Omicron. However, Omicron is still a threat to elderly individuals, especially those with pre-existing health conditions.

In a recent study, Wu, et al., aimed to develop a messenger ribonucleic acid (mRNA) vaccine using the SARS-CoV-2 Omicron variant sequence as a target. The aim was to develop a vaccine capable of generating nAbs in multiple animal models (Figure 1 – similar results were seen in Syrian hamsters and Macaques) against the Omicron variant when compared to other commercially available vaccines.

Figure 1: SOmicron-6P Induces Antigen-Specific Humoral Immune Responses in Mice. (A) Schematic diagram of immunization and sample collection schedule in mice. Female BALB/c mice were immunized on a two-dose schedule with SWT-2P, SOmicron6P, protein subunit vaccine using a dimeric form of the receptor-binding domain of wild-type SARS-CoV-2, or inactivated vaccine of wild-type SARS-CoV-2. (B-C) Percentages of (B) B cells and (C) plasma cells in spleen after immunized with different doses of SOmicron-6P. (D) The Omicron SARS-CoV-2 variant specific IgG antibody titers were determined by ELISA (lower limit of detection (LLOD) = 100). (E) Neutralization titers (NT50) were determined by recombinant vesicular stomatitis 127 virus (VSV)-based pseudovirus (Omicron variant) neutralization assay (LLOD = 150). (F) SARS-CoV-2 Omicron 50% virus-neutralization titers (VNT50) were determined by a plaque reduction neutralization test (LLOD = 150). Data are shown as mean ± SEM. Significance was calculated using one-way ANOVA with multiple comparisons tests (n.s., not significant, *p < 0.05, **p < 0.01, ***p < 132 0.001, ****p < 0.0001) (Wu, et al., 2022).

In the present study, the researchers designed and synthesised mRNA based off of the original SARS-CoV-2 strain and the Omicron variant. The mRNAs were then encapsulated in lipid nanoparticles (LNPs) in order to produce the vaccine.

The study presented the development of a Omicron-specific vaccine which provided protection in naïve animals, improving on existing mRNA vaccines with boosters.

NB to note: bioRxiv is a preprint server which publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, or guide clinical practice or treated as established information.

 

Journal article: Wu, Y., et al. 2022. Omicron-specific mRNA vaccine elicits potent immune responses in mice, hamsters, and nonhuman primatesbioRxiv

 Summary Stefan Botha

 
 
 
 
 
 
International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation