Improved COVID-19 vaccine shows promise against Omicron in models

A recent study published in the journal Science Translational MedicineUS researchers designed a bivalent coronavirus disease 2019 (COVID-19) vaccine on a messenger ribonucleic acid (mRNA) platform.

This mRNA-lipid nanoparticle (LNP) vaccine encoded the full-length nucleocapsid (N) protein of Wuhan-Hu1, the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They assessed its immunogenicity, Effectiveness Against all SARS-CoV-2 variants (VOCs) of concern alone and in combination with mRNA-based vaccines based on the spike (S) protein currently in clinical use in mouse and hamster models.

study: Dual spike and nucleocapsid mRNA vaccination confers protection against SARS-CoV-2 Omicron and Delta variants in preclinical modelsImage credit: Orpheus FX / Shutterstock

Background

All COVID-19 vaccines against SARS-CoV-2 infection target the SARS-CoV-2 S protein or its receptor binding domain (RBD) to elicit potent neutralizing antibody (nAb) responses I’m doing it. Researchers therefore believe that vaccines targeting more conserved SARS-CoV-2 proteins or multivalent vaccines offer broader protection against emerging highly mutated SARS-CoV-2 variants. I hypothesized that. The SARS-CoV-2 N protein is a highly conserved and potent immunogen that has been shown to elicit strong T-cell responses, making it an ideal candidate for incorporation into next-generation vaccines. increase.

About research

In this study, researchers evaluated the immunogenicity of mRNA-N vaccine formulations in BALB/c mice. They created two groups of 7 mice each and administered either phosphate-buffered saline (PBS) (mock) or 1 μg m-RNA N vaccine at week 0 (prime) and week 3 (booster). were vaccinated intramuscularly (IM). After primary vaccination, the team collected serum samples for antibody analysis. After booster vaccination, they euthanized the mice for further immunological analysis.

The team examined T-cell responses in splenocytes by flow cytometry. Similarly, they measured her N-specific T-cell responses by intracellular cytokine staining (ICS) of splenocytes. Additionally, an interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay was performed to assess mRNA-N vaccine-induced T cell responses.

In addition, the researchers used an enzyme-linked immunosorbent assay (ELISA) to determine antibody titers for N-specific binding immunoglobulin G (IgG). The team performed a similar vaccine evaluation against his SARS-CoV-2 Delta VOC in Syrian hamsters.

Survey results

Although mRNA-N was highly immunogenic, it only moderately controlled SARS-CoV-2 infection. However, mRNA-S+N combination vaccination was more potent in regulating SARS-CoV-2 Delta and Omicron VOC in the lungs of infected mice than mRNA-S alone, providing additional protection against both variants. and decreased the viral load in the upper respiratory tract. Tract (URT).

Dual spike and nucleocapsid mRNA vaccination confers protection against SARS-CoV-2 Omicron and Delta variants in preclinical models

This study provided considerable evidence implicating T cells in mRNA-S+N vaccine protection against SARS-CoV-2 variants. For example, mRNA-N alone induced modest protection against both SARS-CoV-2 and Delta strains. Neutralizing antibodySimilarly, in vivo Cell depletion analysis suggested the potential involvement of differentiated 8 (CD8+) T cell clusters in the immunoprotection induced by the mRNA-S+N vaccine. The authors performed an antigen-specific immunity assay and observed that the induction of N-specific immunity accompanied by enhanced S-specific immunity helps the bivalent mRNA vaccine to initiate a more vigorous immune response. did.

Interestingly, the mRNA S-based vaccine and the combination vaccine (mRNA-S+N) had similar mRNA-S doses but enhanced S-specific immunity. One hypothesis is that a cross-priming effect occurred between N and S antigen After vaccination with mRNA-S+N vaccine. Also, mRNA-N co-immunity may have induced an immune environment that promoted the development of S-specific immunity. However, future studies should investigate all events following mRNA-S+N vaccination, including antigen presentation and stimulation of innate and inflammatory responses.

Conclusion

This study demonstrates that the mRNA-LNP platform has been tested and has shown a favorable safety profile in multiple clinical studies in humans, making this approach rapidly clinical against the yet-to-be-emerged SARS-CoV-2 VOC. Previous studies have demonstrated challenges in designing COVID-19 vaccines using VOC-specific sequences. The vaccine tested in the current study had mRNA-N and mRNA-S amino acid sequences from Wuhan-Hu-1. Still, it elicited strong protection against both Delta and Omicron VOCs. This was exemplary. Further testing of combination vaccine approaches in non-human primates (NHPs) will provide more opportunities to evaluate their safety and efficacy.

In SARS-CoV-2 VOC-infected hamsters, the combined mRNA-S+N vaccine induced strong viral control in the lungs. However, its additive antiviral effect appeared to decrease with URT. Therefore, future studies should investigate heterologous vaccination approaches involving different vaccine platforms and routes of immunization. For example, vaccination strategies that improve the protection of URT against VOCs using IM, intranasal, and oral delivery routes.