SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum, but evades most convalescent serum and therapeutic antibodies.
PMID: 35380448
2022
Science translational medicine
Discussion: Some substitutions specific to the Omicron spike protein near the prefusion-stabilizing 2P mutations (K986P and V987P) used in mRNA vaccines could help stabilize conformations that expose shared epitopes between the D614G vaccine antigen and Omicron.
Evolution of the SARS-CoV-2 spike protein in the human host.
Method: The following variant spikes were made (SA, Alpha and mink) (all mutations listed with reference to the NCBI sequence YP_009724390.1): 2P Alpha (Delta69-70, Delta144, N501Y, A570D, D614G, P681H, T716A, S982A, D1118H, and K986P, V987P), FUR2P Alpha (Delta69-70, Delta144, N501
Method: The variant spikes were stabilised in the pre-fusion conformation (K986P and V987P) with the furin-cleavage site ([PH]RRAR) either intact ('2P' constructs) or mutated to the uncleavable sequence PSRAS ('FUR2P' constructs).
Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability.
PMID: 35163572
2022
International journal of molecular sciences
Introduction: The S-GSAS construct showed similar structural, antigenic, and stability behavior as the S-GSAS/PP construct, which included the K986P and V987P mutations.
Method: The glycosylated microenvironment for atomistic models of the simulation trajectories was mimicked by using the structurally resolved glycan conformations for 22 most occupied N-glycans in each as determined in the cryo-EM structures of the SARS-CoV-2 spike S trimer in the closed state (K986P/V987P,) (pdb id 6VXX) and open state (pdb id 6VYB), and the cryo-EM structure SARS-CoV-2 spike trimer (K986P/V987P) in the open state (pdb id 6VSB).
Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.
Method: In the second study, cynomolgus macaques (n=5) were were immunized twice with 50 mug of S-2P mRNA-LNP (encoding the transmembrane spike protein stabilized with K986P and V987P mutations) and boosted once with 100 mug of RBD-scNP, NTD-scNP and S2P-scNP adjuvanted with 5 mug of 3M-052 aqueous formulation admixed with 500 mug of alum in PBS.
Method: The S-2P mRNA was designed based on the SARS-CoV-2 spike (S) protein sequence (Wuhan-Hu-1) and encoded the full-length S with K986P and V987P amino acid substitutions.
Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern.
Method: It is the ectodomain of SARS-CoV-2 spike protein expressed in HEK293 cells, which contains amino acids Val16 - Pro1213 of Spike (GenBank: QHD43416.1) with T4 fibritin trimerization motif, a polyhistidine tag at the C-terminus, proline substitutions (F817P, A892P, A899P, A942P, K986P, V987P) and alanine substitutions (R683A and R685A) to stabilize the trimeric pre-fusion conformation, and mutations identified in the Omicron variant (A67V, HV69-70del, T95I, G142D, VYY143-145del, N211del,
Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.
Method: SARS-CoV-2 S protein expression plasmids were constructed to encode the ectodomain of S protein S(D614G) or SAlpha (residues 1-1208, with a mutated furin cleavage site and K986P/V987P substitutions) followed by a T4 fold on the trimerization domain and a polyhistidine purification tag.
Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants.
Discussion: Three of the six COVID-19 vaccines currently in use worldwide, namely Moderna mRNA-1273, BioNTech BNT162b2, and Janssen Ad26.COV2.S, each express S harboring K986P and V987P substitutions (2P) within a loop abutting the central helix of the S2' membrane fusion machinery.
An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection.
Method: SARS-CoV-2 spike ectodomains (residues 1-1211) were cloned into the vector containing mutations of interest, in addition to two proline mutations in S2 (K986P, V987P), a C-terminal foldon trimerization tag, and a C-terminal His6-tag.
SARS_CoV_2 mutation literature information.
PMID: 
2022
Science translational medicine
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