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Structural Dynamic Impacts of Mosaic SARS-CoV-2 Spike Heterotrimer

ABSTRACT: Polyvalent vaccines are being widely investigated for their broadening immune responses against rapidly mutating pathogens. In response to the emergence of highly infectious SARS-CoV-2 variants of concern, bivalent mRNA vaccines, which encode the original Hu-1 variant and Omicron variant, have demonstrated a novel approach to achieving polyvalency. However, the structural basis for immunogen display in mRNA vaccines has been less studied: specifically, whether protomers from different SARS-CoV-2 variants can co-assemble into mosaic heterotrimer and how this might affect trimer stability, dynamics and antigenicity. To investigate this, we successfully purified mosaic spike assemblies from co-expression of genetically close strains: Omicron BA.2 and XBB (OX), and distant strains: Omicron BA.2 and original Hu-1 G614 (OG). The trimer stability and integrity are well maintained in the mosaic spike trimers. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) and biolayer-interferometry were used to investigate the mosaic spike dynamics and impacts on antigenicity and receptor binding. These are important issues to investigate as numerous vaccine studies employing gene delivery such as with the mRNA-lipid nanoparticle modality that are pursuing pan-coronavirus or universal influenza vaccines rely upon co-administration of panels of antigen variants. The study provides valuable information to help understand the impact of co-transfection and co-expression on the combinatorial antigens that are produced in these scenarios.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Covid-19

SUBMITTER: Chengbo Chen

LAB HEAD: Kelly Lee

PROVIDER: PXD060785 | Pride | 2025-09-17

REPOSITORIES: Pride

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			Action	DRS
	G614_MSMS.raw	Raw
	HDX_G614_Homotrimer.zip	Other
	HDX_OG_Heterotrimer.zip	Other
	HDX_OX_Heterotrimer.zip	Other
	HDX_Omicron_Homotrimer.zip	Other

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