- NVX-CoV2373 is a variant of the SARS-CoV-2 spike protein (S) created by mutating
 the furin cleavage site to be resistant to cleavage and using 2-prolines substitutions.

Carnegie Mellon University

Description from Literary Review:

NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimetric full-length SARS-CoV2 spike glycoproteins and Matrix M1 adjuvant. A randomized, placebo-control, phase 1-2 trial was conducted on 131 healthy adults.  It has high immunogenicity and high levels of neutralizing antibodies. On September 24, 2020, phase 3 clinical trials began and immunized 10,000 people in the next 4-6 weeks. This took place at the Nucleus Network in Herston, Queensland and Melbourne, Victoria.
This vaccine candidate is a recombinant nanoparticle vaccine constructed from full-length wild-type SARS-CoV-2 spike glycoprotein. It includes Matrix M1 Which is a saponin based adjuvant made by Novavax. The rSARS-CoV-2 and Matrix M1 parts were mixed just before use. This vaccine is favorable because it can be stored between 2°C and 8°C, allowing for easy preservation and, therefore, distribution (Novavax Initiates Phase 3 Efficacy Trial of COVID-19 Vaccine in the United Kingdom | Novavax Inc. - IR Site, n.d.).
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NVX-CoV2373 Vaccine by Novavax Inc.

Tian, J., Patel, N., Haupt, R., Zhou, H., Weston, S., Hammond, H., . . . Smith, G. (2020). SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. MedRxiv. doi:10.1101/2020.06.29.178509

Link: https://www.biorxiv.org/content/10.1101/2020.06.29.178509v1

SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

Structure of double mutant NVX-CoV2373 

- Preserving the structural integrity of the protein in stressful environments is important for global distribution.
- pH extremes, prolonged agitation, freeze/thaw cycles, or elevated temperature had no effect on hACE2 receptor binding. Only oxidizing conditions with hydrogen perozide reduced binding by 8-fold
- NVX-Cov2327 had better thermal stability than wild type S protein

Stability of  NVX-CoV2373

- Production of  titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 
- T-cell responses including CD4+ and CD8+ T cells, CD4+T and follicular helper T cells (Tfh)

NVX-CoV2372 Targeted Responses

NVX-CoV2373 attained 50% saturation of hACE2 binding at 2-fold lower concentration than the wild type protein and the single-mutated BV2365. Binding was also specific to hACE2.

NVX-CoV2373 Binding Affinity

- Anti-spike immunoglobulin G (IgG) ELISA (Days 0, 7, 21, 28, and 35)
- Wild-type virus microneutralization assay (MN) with an inhibitory concentration of > 99% (MN IC>99) (Days 0, 21, and 35)
- Intracellular cytokine staining of antigen-specific CD4+ T cells (Days 0 and 28).
- Human ACE2 receptor binding inhibition by ELISA 
- peripheral blood mononuclear cells for T-cell responses  

NVX-CoV2373 Immunogenicity Assays

- Generally mild reactogenicity and well tolerated
- After first dosage, the most common side effects were local tenderness and pain while system events were less frequent (headache, fatigue, and myalgia being the most common), but the majority of reported symptoms remained at grade ≤1. 
- After the second dosage, only one participant experienced (mild) fever

NVX-CoV2373 Reactogenicity

- Induced a greater immune response than without the adjuvant: higher levels of neutralizing antibodies and greater T-cell response 
- Dose sparing (induce same level of response with less dosage)

NVX-Cov2373: Benefits of Matrix-M1 Adjuvant

- NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimetric full-length SARS-CoV2 spike glycoproteins and Matrix M1 adjuvant
- Novavax identified this as its candidate with high immunogenicity and high levels of neutralizing antibodies
- September 24, 2020: Phase 3 clinical trials began in the UK and immunize 10,000 people in the next 4-6 weeks
- January 21, 2021: 22,000 volunteers enrolled worldwide

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