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Cell Host Microbe ; 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2237104


SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Cell Rep ; 38(12): 110558, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1797096


Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

COVID-19 , SARS-CoV-2 , Animals , Ferrets , Humans , Membrane Glycoproteins/metabolism , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Tropism , Viral Envelope Proteins
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1728589


Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOC/VOI variants. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.