However, a subset of patients had no detectable nAbs, despite clearly detectable anti-RBD antibodies at titers exceeding 10e3 AU/ml (Fig ?(Fig1E).1E). was quantified using pseudovirus neutralization assay and live computer virus neutralization against the initial SARS LY2090314 CoV-2 strain and the B1.617.2 (Delta) variant. RESULTS Vaccine-induced nAbs are detectable at much lower rates (54%) than estimated in previous seroconversion studies in MM, which did not monitor viral neutralization. In 33% of patients, vaccine-induced antispike RBD antibodies lack detectable neutralizing capacity, including against the B1.617.2 variant. Induction of nAbs is usually affected by race, disease, and treatment-related factors. Patients receiving mRNA1273 vaccine (Moderna) achieved significantly greater induction of nAbs compared with those receiving BNT162b2 (Pfizer; 67% 48%, = .006). CONCLUSION These data show that vaccine-induced antibodies in several patients with MM lack detectable virus-neutralizing activity. Vaccine-mediated induction of nAbs is usually affected by race, disease, vaccine, and treatment characteristics. These data have several implications for the emerging application of booster vaccines in immunocompromised hosts. INTRODUCTION Patients with hematologic malignancies are at an increased risk of contamination with SARS CoV-2 and COVID-19Crelated mortality.1 Multiple myeloma (MM) is a common hematologic malignancy characterized by growth of malignant plasma cells. Initial studies in patients with MM suggested variable serologic response to SARS CoV-2 vaccines with > 80% seroconversion rates.2-6 However, these studies were limited to the detection of antibodies against CoV-2 spike proteins/receptor-binding domain name (RBD)2,4,5 or surrogate assays for competition with binding between RBD and its cellular receptor angiotensin converting enzyme-2.3,6 Neutralizing antibodies (nAbs) are highly predictive of immune protection from symptomatic SARS CoV-2 infection and are the desired targets of vaccination.7 Vaccine-induced nAbs may also provide cross-reactive protection against emergence of variants.8 However, data regarding the induction of SARS CoV-2 nAbs in vaccinated patients with MM and clinical features that affect the induction of these antibodies in these patients are lacking. Understanding the determinants of vaccine-mediated induction of nAbs in patients with MM is critical to developing strategies to protect these patients from SARS CoV-2. In addition, patients with B-cell malignancies such as MM may serve as reservoirs for the generation of viral variants. 9 Optimizing protection of these patients may also therefore be critical for control of the pandemic. CONTEXT Key Objective What is the efficacy of SARS CoV-2 vaccines in inducing antibodies with virus-neutralizing capacity in patients with myeloma? Knowledge Generated Neutralizing antibodies (nAbs) are generated in only 54% of myeloma patients with current RNA vaccines. Induction of nAbs is usually affected by race (higher in Black patients), vaccine (higher with Moderna versus Pfizer), and myeloma therapy (lower with CD38 antibodies). Relevance (Editor-in-Chief Jonathan W. Friedberg, MD. METHODS To evaluate the immune response to SARS CoV-2 vaccination, we obtained blood specimens from 238 patients with MM (patient characteristics are given in the Data Supplement [online only]) receiving SARS CoV-2 vaccines after informed consent approved by the Emory Institutional Review Board. Serologic response to the vaccine was measured with an ELISA to detect antibodies against SARS CoV-2 spike RBD.10,11 Antibodies against nucleocapsid (NC) were monitored to evaluate environmental exposure to the computer LY2090314 virus. In parallel, a pseudovirus neutralization assay was used to detect nAbs.11 Further validation of the assays was performed using a Mesoscale Discovery (MSD) assay for detection of antispike antibodies against SARS CoV-2 and other coronaviruses. In addition, antibodies were also tested for live computer virus neutralization against the initial SARS CoV-2 strain and the current dominant B1.617.2 (Delta) variant.12 See the Data Supplement (online only) for details of methods. RESULTS Overall, RBD-specific antibodies were detected after the second vaccine in 208 of 238 (87%) patients tested, consistent with previous studies2,4 (Fig ?(Fig1A1A and Data Supplement). However, only 128 patients (54%) had SARS CoV-2 nAbs detected by a pseudovirus neutralization assay (Fig ?(Fig1B1B and Data Supplement). Both anti-RBD and nAb titers peaked at 1-2 weeks after second vaccine and declined by LY2090314 3 Rabbit Polyclonal to CAPN9 months (Data Supplement). NC antibodies indicative of prior.