Nanoparticles displaying SARS-CoV-1 and SARS-CoV-2 spikes induce broad antibody responses in animal model Antibody Nanoparticles SARS SARSCoV2 Coronavirus Disease COVID iScience_CP UW WeillCornell UvA_Amsterdam scrippsresearch
Coronavirus disease 2019 vaccines are based on the spike protein of the severe acute respiratory syndrome coronavirus 2 Wuhan-Hu-1 strain. Mutant SARS-CoV-2 variants are less sensitive to immune responses elicited by these vaccines. As such, vaccines incorporating sequence diversity may augment protection against novel SARS-CoV-2 variants.
The study and findings In the present study, researchers leveraged the I53-50 platform to co-display diverse spike proteins and evaluated the immune responses. First, they fused the N-terminus of component A to the C-terminus of the Beta variant’s spike protein through a glycine-serine linker. Then, after purification, the spike-A fusion protein was mixed with an equimolar quantity of component B for assembly.
A pseudovirus neutralization assay was performed to assess the neutralization of SARS-CoV-2 variants of concern , SARS-CoV-1, and animal CoVs . Ancestral spike NPs induced the most potent nAbs against ancestral strain but weaker against variants, with substantially lower titers against Beta and Omicron variants.
BALB/c mice and rabbits were immunized with the cocktail or mosaic NPs at 0, 4, and 12 weeks and bled at zero- and two weeks post-immunization. The authors re-analyzed data from previous studies that used the SARS-CoV-2 soluble spike antigen and NPs to immunize rabbits and mice using the same dosing regimen. SARS-CoV-2 spike NPs elicited three-fold greater neutralization than other immunogens in mice, albeit this was not statistically significant.
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