The proteins were visualized by luminescent substrate (Millipore) on iBright CL1000. == Statistical Analysis == All experiments were in technical duplicates or triplicates. all of which have been shown to be highly effective. The mRNA-based vaccines were 94-95% effective in avoiding COVID-19 (1) whereas the adenoviral vector-based J&J vaccine experienced 66.9% 18α-Glycyrrhetinic acid efficacy in preventing moderate to severe disease (2). However, the ongoing emergence of highly transmissible variants with mutations in the spike protein raises concerns concerning possible decreases in vaccine performance due to spike protein antigenic variability. SARS-CoV-2 variants have been classified by the World Health Corporation (WHO) based on improved transmissibility and/or pathogenicity as variants of concern (VOC; Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.248), Delta (B.1.617.2) and variants of interest (VOI; Epsilon (B.1.427/B.1.429), Iota (B.1.526), and Delta in addition (AY.1) and Lambda (C.37) (3). The improved transmissibility and/or pathogenicity of the variants 18α-Glycyrrhetinic acid is due, at least in part, to mutations in the spike protein RBD that increase its affinity for ACE2 on target cells. Mutations in the Beta, Gamma and Delta variant spike RBDs have been shown to cause partial resistance to neutralization from the serum antibodies of vaccinated and convalescent individuals and restorative monoclonal antibodies (411). This study measured the neutralization titers of serum antibodies from individuals immunized with three U.S. FDA Emergency use authorization vaccines (BNT162b2, mRNA-1273 and Ad26.COV2.S) against viruses with the VOC and Lambda spike proteins. The study organizations were controlled for age, clinical co-morbidity, history of pre-vaccination illness and sera were collected on related days post-vaccination. The results demonstrate a high level of cross-neutralization by antibodies elicited by BNT162b2 and mRNA-1273 within the variants but significantly decreased neutralization by those elicited from 18α-Glycyrrhetinic acid the solitary dose Ad26.COV2.S. == Materials and Methods == == Clinical Study == Convalescent sera were collected 32-57 days post-symptom onset. For the early time-point, BNT162b2 and Moderna-vaccinated sera were collected on day time 28 and 35, respectively, 7 days post-second immunization. For the later on time-point, BNT162b2-vaccinated sera were collected 52-110 (mean 90) day time post-second immunization and mRNA-1273-vaccinated sera were collected 44-105 (mean 80) days post-second immunization. Ad26.COV2.S-vaccinated sera were collected 57-115 (mean 82) days post-immunization (Supplementary Table 2). The medical study was carried out in the NYU Vaccine Center with participants written consent under IRB-approved protocols (18-02035 and 18-02037). REGN10933 and REGN10987 were generated as previously explained (7). == Plasmids == pLenti.GFP.NLuc is based on pLenti.CMV.GFP.puro containing a GFP/nanoluciferase cassette separated by a picornavirus P2A self-processing amino acid motif cloned into the BamH-I and Sal-I sites (Addgene plasmid #17448, provided by Eric Campeau and Paul Kaufman). pcCOV2.19S is based on pCDNA6 in which the CMV promoter drives transcription of a synthetic, codon-optimized SARS-CoV-2 spike gene based on Wuhan-Hu-1/2019 having a termination codon at position 1255 that deletes the carboxy-terminal 19 amino acids (12). Spike mutations p45 were launched into pcCOV2.19.D614GS by overlap extension PCR and confirmed by DNA nucleotide sequencing. Plasmids used in the production of lentiviral pseudotypes (pMDL and HIV-1 Rev manifestation vector pRSV.Rev) have been previously explained (12). sACE2-Nluc was launched into pcDNA6 by overlap extension PCR and confirmed by DNA nucleotide sequencing. == Cells == HEK293T cells were cultured in Dulbeccos revised Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/S) at 37C in 5% CO2. ACE2.293T are clonal cell-lines that stably express a transfected human being ACE2. The cells were taken care of in DMEM/1 g/ml puromycin/10% FBS/1% P/S. == SARS-CoV-2 Spike Lentiviral 18α-Glycyrrhetinic acid 18α-Glycyrrhetinic acid Pseudotypes == Lentiviruses pseudotyped by variant SARS-CoV-2 spikes were produced as previously reported (12). Briefly, pseudotyped virus shares were generated by cotransfection of 293T cells with pMDL, pLenti.GFP-NLuc, pcCoV2.S-19 and.