Determinants of Neutralizing Antibody Response After SARS CoV-2 Vaccination in Patients With Myeloma

Abstract

PURPOSE Vaccine-induced neutralizing antibodies (nAbs) play a critical role in protection from SARS CoV-2. Patients with B-cell malignancies including myeloma are at increased risk of COVID-19–related mortality and exhibit variable serologic response to the vaccine. The capacity of vaccine-induced antibodies in these patients to neutralize SARS CoV-2 or its variants is not known. METHODS Sera from 238 patients with multiple myeloma (MM) undergoing SARS CoV-2 vaccination were analyzed. Antibodies against the SARS CoV-2 spike receptor-binding domain (RBD) and viral nucleocapsid were measured to detect serologic response to vaccine and environmental exposure to the virus. The capacity of antibodies to neutralize virus was quantified using pseudovirus neutralization assay and live virus neutralization against the initial SARS 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 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% v 48%, P = .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 affected by race, disease, vaccine, and treatment characteristics. These data have several implications for the emerging application of booster vaccines in immunocompromised hosts.

Antibody and T‐cell responses by ultra‐deep T‐cell receptor immunosequencing after COVID‐19 vaccination in patients with plasma cell dyscrasias

“…Using commercially available anti‐spike antibody testing, we observed that ~85% of our patients with PCD mounted a positive serological response within 6 months of completing the initial vaccination series, comparable to other previous studies. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 In studies assessing neutralising antibodies, the serological response has been lower, ranging from 41% to 74%. 12 , 19 , 20 , 21 , 22 Although the presence and titre of neutralising antibodies may more directly reflect viral protection, these assays are not widely available in clinical practice.…”

“… 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 In studies assessing neutralising antibodies, the serological response has been lower, ranging from 41% to 74%. 12 , 19 , 20 , 21 , 22 Although the presence and titre of neutralising antibodies may more directly reflect viral protection, these assays are not widely available in clinical practice. In most studies, good correlation has been observed between spike receptor‐binding domain (RBD) IgG antibody titres and inhibition capacity of neutralising antibodies, including in studies of MM 12 , 23 , 24 and for different anti‐spike RBD IgG assays utilised in this study.…”

“… 12 , 19 , 20 , 21 , 22 Although the presence and titre of neutralising antibodies may more directly reflect viral protection, these assays are not widely available in clinical practice. In most studies, good correlation has been observed between spike receptor‐binding domain (RBD) IgG antibody titres and inhibition capacity of neutralising antibodies, including in studies of MM 12 , 23 , 24 and for different anti‐spike RBD IgG assays utilised in this study. 25 , 26 , 27 , 28 , 29 As such, we postulate that the presence and level of total anti‐spike binding IgG antibodies may be a surrogate marker for humoral immunity to COVID‐19 infection, acknowledging, however, that a subset of patients with positive RBD antibodies may have impaired neutralisation ability as highlighted in other studies.…”

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers

“…For the initial analysis of BoAb assay, we used samples from Nooka et al, 33 who studied the neutralization determinants in myeloma patients. With this cohort, we observed that results in the BoAb assay strongly correlated with both live virus neutralization (Wuhan R 2 = 0.82 and p=<0.001; Delta R 2 = 0.80 and p=<0.001) and pseudovirus neutralization results (Wuhan R 2 = 0.72 and p=<0.001; Delta R 2 = 0.66 and p=<0.001).…”

“…Neutralization activities against SARS-CoV-2 WT (Wuh-1) and Delta (B.1.617.2) strains were measured in a single-round-of-infection assay with pseudo viruses, as previously described 33 . Briefly, to produce SARS-CoV-2 WT and Delta pseudoviruses, an expression plasmid bearing codon optimized SARS-CoV-2 full-length S plasmid (parental sequence Wuhan-1, Genbank #: MN908947.3) was co-transfected into HEK293T cells (ATCC#CRL-11268) with plasmids encoding non-surface proteins for lentivirus production and a lentiviral backbone plasmid expressing a Luciferase-IRES-ZsGreen reporter, HIV-1 Tat and Rev packing plasmids (BEI Resources) and pseudoviruses harvested after 48 hours of post transfection and performed titration.…”