Newcastle Disease Virus-Like Particle Displaying Prefusion Stabilized SARS-CoV-2 Spike and Its Use

SARS-CoV-2 has resulted in a global pandemic, sparking urgent vaccine development efforts. The trimeric SARS-CoV-2 spike stabilized in its prefusion conformation by the addition of 2 proline mutations (“SARS-CoV-2 S2P”) is the antigenic basis of SARS-CoV-2 vaccines that are currently authorized for use in the United States.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) sought to optimize the presentation of SARS-CoV-2 S2P to the immune system with the goal of eliciting a strong and durable immune response. The researchers designed fusion proteins made of SARS-CoV-2 S2P and Newcastle Disease fusion transmembrane domain and cytosolic tail which form virus like particles (VLPs) displaying the SARS-CoV-2 S2P on the particle surface.

SARS-CoV-2 S2P displaying Newcastle Disease virus-like particles (“S2P-NDVLP”) elicited a robust immune response two weeks after a single immunization. The S2P-NDVLP also elicited an improved immunogenicity despite delivering a lower number of SARS-CoV-2 S2P antigens than the soluble SARS-CoV-2 S2P to which they were compared. This improved immunogenicity is likely due to several characteristics of S2P-NDVLPs such as the mass and large size of the VLP particle that can result in a strong immune response and increase uptake of the S2P by dendritic cells Displaying multiple SARS-CoV-2 S2P on a single particle could allow multiple B-cell receptors on individual B cells to bind that single particle, thereby cross-linking the B-cell receptors and activating those B cells. Lastly, the lipid membrane of the S2P-NDVLP could allow the immunogen to more closely mimic the real virus and boost immune response.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404. . ..