Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy

Abstract

Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8). Individuals post-CAR-T-cell therapy were in remission. We tested for antibodies to 4 vaccine strains at baseline and ≥1 time point after IIV using neutralization and hemagglutination inhibition assays. An antibody response was defined as a ≥4-fold titer increase from baseline at the first post-vaccine time point. Baseline A(H1N1) titers in the CAR-T cohorts were significantly lower compared to controls. Antibody responses to ≥1 vaccine strain occurred in 2 (29%) individuals before CAR-T-cell therapy; one individual maintained a response for >3 months post-CAR-T-cell therapy. Antibody responses to ≥1 vaccine strain occurred in 6 (40%) individuals vaccinated after CAR-T-cell therapy. An additional 2 (29%) and 6 (40%) individuals had ≥2-fold increases (at any time) in the pre- and post-CAR-T cohorts, respectively. There were no identified clinical or immunologic predictors of antibody responses. Neither severe hypogammaglobulinemia nor B-cell aplasia precluded antibody responses. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B-cell aplasia. Larger studies are needed to determine correlates of vaccine immunogenicity and durability in CAR-T-cell therapy recipients.

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

“…However, factors that determine the ability to mount immune response to vaccination after CAR T-cell therapy are not well understood. In a recent study, neither B cell aplasia or low IgG predicted vaccine immunogenicity and thus should not preclude vaccination after CAR T-cells [58]. While patients treated with CAR T-cells had lower rate of seroprotection after vaccinations, some patients could develop adequate immune responses.…”

“…B-cell aplasia, plasma cell depletion, and resultant hypogammaglobulinemia are inevitable side effects of CD19/BCMA CAR T-cells and could predispose patients to infectious complications [55,56]. [57,58]. In conclusion, both patients and CAR T-associated factors lead to a cumulative immunosuppressive state, which predisposes CAR T-cell recipients to infections.…”

Real-time SARS-CoV-2 diagnostic and variants tracking over multiple candidates using nanopore DNA sequencing

“…1 million concatemers sequenced corresponds to 9 million monomers; Figure S1 and Fig. 3 E), such that a large number of candidates can be potentially screened like in previous population-scale diagnostics efforts based on the use of Illumina instruments 3 – 5 .

Figure 3 SARS-CoV-2 diagnostics assay with Nanopore DNA sequencing.

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“…With the aim of taking advantage of the viral nucleic acid targeting diagnostics but at the same time increasing the number of candidates’ through-put, strategies based on the use of massive parallel DNA sequencing for population-scale diagnostics were proposed 3 – 5 . These efforts rely on (1) the incorporation of DNA molecular barcodes during sample preparation; (2) pooling barcoded samples for an “in-one-run” diagnostics assay by the use of massive parallel DNA sequencing; (3) stratification of diagnostics’ outcome with the help of bioinformatics processing.…”