Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92 · 3% of patients received the primer vaccine, 70 · 8% received one monovalent booster, but only 30 · 1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR = 0 · 61, p = 0 · 024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed.

Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T-cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92·3% of patients received the primer vaccine, 70·8% received one monovalent booster, but only 30·1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR=0·61, P=0·024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed. Highlights: COVID-19 booster vaccinations increase antibody levels and maintain T-cell responses against SARS-CoV-2 in patients receiving various anti-cancer therapiesBooster vaccinations reduced all-cause mortality in patientsA significant proportion of patients remain unboosted and strategies are needed to encourage patients to be up-to-date with vaccinations.

The T-Cell Response to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease is Augmented with Anti-TNF Therapy.

T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 vaccination in inflammatory bowel disease patients are poorly correlated. T-cell responses are preserved by most biologic therapies, but augmented by anti-tumor necrosis factor (anti-TNF) treatment. While anti-TNF therapy blunts the antibody response, cellular immunity after vaccination is robust.

Longitudinal SARS-CoV-2 mRNA Vaccine-Induced Humoral Immune Responses in Patients with Cancer.

Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P < 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection. SIGNIFICANCE: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.

Urine proteomic analysis: use of two-dimensional gel electrophoresis, isotope coded affinity tags, and capillary electrophoresis.

The identities and abundance levels of proteins excreted in urine are not only key indicators of diseases associated with renal function but are also indicators of the overall health of individuals. Urine specimens are readily available and provide a noninvasive means to assess and diagnose many disease states. Proteins in urine originate from two sources: the ultrafiltrate of plasma, and those that are shed from the urinary tract. The protein concentration in urine excreted from a normal adult is approximately 150 mg/day, and is typically not greater than 10 mg/100 mL in any single specimen. Following precipitation, concentration, and fractionation methods, proteins of interest from urine samples can be separated, identified, and quantified. One of the most commonly used techniques in the field of urine proteomics is gel electrophoresis followed by identification with mass spectrometry and protein database search algorithms. In this chapter, two-dimensional gel electrophoresis (2-DE) will be discussed, along with less frequently applied techniques, such as isotope coded affinity tags (ICAT) and capillary electrophoresis (CE). Publications discussing the application of these techniques to urine proteomic analyses of healthy individuals and urinary disease biomarker discovery will also be summarized.

A rapid and simple high-performance liquid chromatography assay for the leflunomide metabolite, teriflunomide (A77 1726), in renal transplant recipients.

Leflunomide (Arava), a drug with immunosuppressive and antiviral effects, is being used in renal transplant recipients, primarily for its action against BK polyomavirus (BKV), which affects 1% to 10% of renal transplant recipients and often causes failure of grafted kidneys. Leflunomide effects are solely due to an active metabolite, teriflunomide (formerly A77 1726). Trough blood concentrations of teriflunomide exceeding 40 microg/mL (148 micromol/L) are associated with progressive clearance of BKV. Toxic effects become increasingly apparent at higher concentrations. We have developed a rapid, simple, and robust high-performance liquid chromatography (HPLC) method for therapeutic monitoring of teriflunomide in renal transplant recipients. Sample preparation is rapid, and each HPLC separation takes about 7 minutes. Intraday and interday coefficients of variation were 1.5% or less and 5.6% or less, respectively. The method was linear to 200 microg/mL (740 micromol/L), which is well above teriflunomide concentrations that are likely to be observed.

Repeatability of chemical cytometry: 2-DE analysis of single RAW 264.7 macrophage cells.

This report presents the use of 2-DE with ultrasensitive fluorescence detection as a chemical cytometry tool to characterize the protein and biogenic amine content of single cells from the RAW 264.7 murine macrophage cell line. Cells were sorted by cell cycle prior to 2-DE analysis. Cells in the G2/M phase of the cell cycle were aspirated into the first-dimensional capillary and lysed. The cellular contents were fluorescently labeled and first separated by capillary sieving electrophoresis (CSE). Over 380 fractions were transferred from the first-dimensional capillary to the second-dimensional capillary, where components were further separated by MEKC and detected by laser-induced fluorescence. Twenty-five spots common to the four electropherograms were fit with a 2-D Gaussian surface to determine spot position, width, and amplitude. The RSD in CSE mobility was 1.0 +/- 0.6%. The mean uncertainty in spot position was 1.3 times larger than the mean spot width in the CSE dimension. The average SD in MEKC migration time was 0.37 +/- 0.13 s, which is smaller than the average spot size in this dimension. Spot capacity was 200. The RSD in spot amplitude was 50%, reflecting a large cell-to-cell variation in component expression.