key: cord-0760492-4vmmvttd authors: Rosati, Margherita; Terpos, Evangelos; Agarwal, Mahesh; Karalis, Vangelis; Bear, Jenifer; Burns, Robert; Hu, Xintao; Papademetriou, Demetrios; Ntanasis‐Stathopoulos, Ioannis; Trougakos, Ioannis P.; Dimopoulos, Meletios‐Athanasios; Pavlakis, George N.; Felber, Barbara K. title: Distinct neutralization profile of spike variants by antibodies induced upon SARS‐CoV‐2 infection or vaccination date: 2021-11-05 journal: Am J Hematol DOI: 10.1002/ajh.26380 sha: f48478dd1d01a95e0429426cb04a5f4b16999574 doc_id: 760492 cord_uid: 4vmmvttd nan ). We found a strong direct correlation (Spearman r = 0.8586, p < .0001), supporting the notion that individuals with robust NAb against WA1 also strongly neutralize Delta. vaccine-or infection-induced SARS-CoV-2 immunity 16,17 by the circulating Delta strain may occur in individuals with low anti-WA1 antibodies. Our data indicate that a WA1-based booster vaccination will greatly improve anti-Delta immune response. To further characterize the WA1 vaccine-induced and the infection-induced Delta-specific antibodies, we compared the ratio of the respective NAb and binding antibodies in the three cohorts ( Figure 1I ). Interestingly, compared to the naïve vaccine recipients, we found significant higher ratios in the convalescent cohort and in the convalescent vaccine recipients. These data support the conclusion SARS-CoV-2 booster vaccination using WA1 is being implemented in many countries to increase the anti-Spike antibody titers, and our data support its merit to improve anti-WA1 antibody magnitude and thereby increased ability to recognize Delta. However, our data also show that the magnitude alone is not sufficient to neutralize effectively current SARS-CoV-2 variants of concern. Thus, future booster vaccinations with variant Spike vaccines, including Delta and Beta, should be considered to increase the breadth of the immune responses. The nucleic acid vaccine platform offers the necessary versatility to rapidly adapt to emerging variants of concern, which need to be considered in the future to improve vaccine efficacy. Systemic IL-15, IFN-gamma, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients Anti-SARS-CoV-2 antibody responses in convalescent plasma donors are increased in hospitalized Patients; Subanalyses of a phase 2 clinical study SARS-CoV-2 antibody kinetics eight months from COVID-19 οnset: persistence of spike antibodies but loss of neutralizing antibodies in 24% of convalescent plasma donors Control of SARS-CoV-2 infection after spike DNA or spike DNA+protein co-immunization in rhesus macaques Convergent antibody responses to SARS-CoV-2 in convalescent individuals Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2: a phase 1 randomized clinical trial Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants Reduced sensitivity of SARS-CoV-2 variant delta to antibody neutralization Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19 mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies Covid-19 breakthrough infections in vaccinated health care workers Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections The authors thank D. Esposito (Protein Expression lab; NCI) for SARS-CoV-2 Spike-RBD proteins; members of the Felber and Pavlakis labs for discussion, and T. Jones for assistance. This work was supported by funding from the Intramural Research Program, National