Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab.

BACKGROUND: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses. METHODS: We conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum. RESULTS: Forty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses. CONCLUSIONS: Treatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.

Improved imaging using Mn He-α x rays at OMEGA EP.

In this paper, we report on a crystal based x-ray imaging system fielded at the OMEGA EP laser facility. This new system has a pointing accuracy of +/100 µm, a temporal resolution down to 100 ps (depending on backlighter characteristics), variable magnification, and a spatial resolution of 21.9 µm at the object plane at a magnification of 15×. The system is designed to use a crystal along the crystal plane that satisfies the Bragg condition for the x ray of interest. The thin crystal is then bent into a spherical geometry and attached to a glass backing substrate to hold it in the diagnostic, and the x rays are imaged onto a charge coupled device. We report on data acquired with the new Los Alamos National Laboratory supplied spherical quartz crystal to image the Mn He-α 6.15 keV line emission.

The Scattered Light Time-history Diagnostic suite at the National Ignition Facility.

The Scattered Light Time-history Diagnostic (SLTD) is being implemented at the National Ignition Facility (NIF) to greatly expand the angular coverage of absolute scattered-light measurements for direct- and indirect-drive inertial confinement fusion (ICF) experiments. The SLTD array will ultimately consist of 15 units mounted at a variety of polar and azimuthal angles on the NIF target chamber, complementing the existing NIF backscatter suite. Each SLTD unit collects and diffuses scattered light onto a set of three optical fibers, which transport the light to filtered photodiodes to measure scattered light in different wavelength bands: stimulated Brillouin scattering (350 nm-352 nm), stimulated Raman scattering (430 nm-760 nm), and ω/2 (695 nm-745 nm). SLTD measures scattered light with a time resolution of ∼1 ns and a signal-to-noise ratio of up to 500. Currently, six units are operational and recording data. Measurements of the angular dependence of scattered light will strongly constrain models of laser energy coupling in ICF experiments and allow for a more robust inference of the total laser energy coupled to implosions.

Characterization of shaped Bragg crystal assemblies for narrowband x-ray imaging.

X-ray imaging using shaped crystals in Bragg reflection is a powerful technique used in high-energy-density physics experiments. The characterization of these crystal assemblies with conventional x-ray sources is very difficult because of the required angular resolution of the order of ∼10 µrad and the narrow bandwidth of the crystal. The 10-J, 1-ps Multi-Terawatt (MTW) laser at the Laboratory for Laser Energetics was used to characterize a set of Bragg crystal assemblies. The small spot size (of the order of 5 µm) and the high power (>1018 W/cm2) of this laser make it possible to measure the spatial resolution at the intended photon energy. A set of six crystals from two different vendors was checked on MTW, showing an unexpectedly large variation in spatial resolution of up to a factor of 4.

A high-resolving-power x-ray spectrometer for the OMEGA EP Laser (invited).

A high-resolving-power x-ray spectrometer has been developed for the OMEGA EP Laser System based on a spherically bent Si [220] crystal with a radius of curvature of 330 mm and a Spectral Instruments (SI) 800 Series charge-coupled device. The instrument measures time-integrated x-ray emission spectra in the 7.97- to 8.11-keV range, centered on the Cu Kα1 line. To demonstrate the performance of the spectrometer under high-power conditions, Kα1,2 emission spectra were measured from Cu foils irradiated by the OMEGA EP laser with 100-J, 1-ps pulses at focused intensities above 1018 W/cm2. The ultimate goal is to couple the spectrometer to a picosecond x-ray streak camera and measure temperature-equilibration dynamics inside rapidly heated materials. The plan for these ultrafast streaked x-ray spectroscopy studies is discussed.

Two-color spatial and temporal temperature measurements using a streaked soft x-ray imager.

A dual-channel streaked soft x-ray imager has been designed and used on high energy-density physics experiments at the National Ignition Facility. This streaked imager creates two images of the same x-ray source using two slit apertures and a single shallow angle reflection from a nickel mirror. Thin filters are used to create narrow band pass images at 510 eV and 360 eV. When measuring a Planckian spectrum, the brightness ratio of the two images can be translated into a color-temperature, provided that the spectral sensitivity of the two images is well known. To reduce uncertainty and remove spectral features in the streak camera photocathode from this photon energy range, a thin 100 nm CsI on 50 nm Al streak camera photocathode was implemented. Provided that the spectral shape is well-known, then uncertainties on the spectral sensitivity limits the accuracy of the temperature measurement to approximately 4.5% at 100 eV.

A new streaked soft x-ray imager for the National Ignition Facility.

A new streaked soft x-ray imager has been designed for use on high energy-density (HED) physics experiments at the National Ignition Facility based at the Lawrence Livermore National Laboratory. This streaked imager uses a slit aperture, single shallow angle reflection from a nickel mirror, and soft x-ray filtering to, when coupled to one of the NIF's x-ray streak cameras, record a 4× magnification, one-dimensional image of an x-ray source with a spatial resolution of less than 90 µm. The energy band pass produced depends upon the filter material used; for the first qualification shots, vanadium and silver-on-titanium filters were used to gate on photon energy ranges of approximately 300-510 eV and 200-400 eV, respectively. A two-channel version of the snout is available for x-ray sources up to 1 mm and a single-channel is available for larger sources up to 3 mm. Both the one and two-channel variants have been qualified on quartz wire and HED physics target shots.

Soft x-ray backlighting of cryogenic implosions using a narrowband crystal imaging system (invited).

A high-performance cryogenic DT inertial confinement fusion implosion experiment is an especially challenging backlighting configuration because of the high self-emission of the core at stagnation and the low opacity of the DT shell. High-energy petawatt lasers such as OMEGA EP promise significantly improved backlighting capabilities by generating high x-ray intensities and short emission times. A narrowband x-ray imager with an astigmatism-corrected bent quartz crystal for the Si Heα line at ∼1.86 keV was developed to record backlit images of cryogenic direct-drive implosions. A time-gated recording system minimized the self-emission of the imploding target. A fast target-insertion system capable of moving the backlighter target ∼7 cm in ∼100 ms was developed to avoid interference with the cryogenic shroud system. With backlighter laser energies of ∼1.25 kJ at a 10-ps pulse duration, the radiographic images show a high signal-to-background ratio of >100:1 and a spatial resolution of the order of 10 µm. The backlit images can be used to assess the symmetry of the implosions close to stagnation and the mix of ablator material into the dense shell.

Soft x-ray backlighting of direct-drive implosions using a spherical crystal imager on OMEGA.

Using a spherically bent quartz crystal for the Si He(α) line at ~1.865 keV, a narrowband x-ray imager has been deployed at the Omega Laser Facility to record backlit images of direct-drive laser implosions. The crystal was cut along the 1011 planes for a 2d spacing of 0.687 nm, resulting in a Bragg angle of 83.9°. Apertures in front of the crystal were used to control the astigmatism of the imaging system. The backlit images show a high signal-to-background ratio of >10:1 with backlighter laser energies ≥1.5 kJ at a 10-ps pulse duration and a spatial resolution of better than 20 µm.

Optical diagnostic suite (schlieren, interferometry, and grid image refractometry) on OMEGA EP using a 10-ps, 263-nm probe beam.

A 10-ps, 263-nm (4ω) laser is being built to probe plasmas produced on the OMEGA EP [J. H. Kelly, L. J. Waxer, V. Bagnoud, I. A. Begishev, J. Bromage, B. E. Kruschwitz, T. E. Kessler, S. J. Loucks, D. N. Maywar, R. L. McCrory et al., J. Phys. IV France 133, 75-80 (2006)]. A suite of optical diagnostics (schlieren, interferometry, and grid image refractometry) has been designed to diagnose and characterize a wide variety of plasmas. Light scattered by the probe beam is collected by an f/4 catadioptric telescope and a transport system is designed to image with a near-diffraction-limited resolution (~1 - µm full width at half maximum) over a 5-mm field of view to a diagnostic table. The transport system provides a contrast greater than 1 : 10(4) with respect to all wavelengths outside of the 263 ± 2 nm measurement range.

Shell trajectory measurements from direct-drive implosion experiments.

A technique to measure the shell trajectory in direct-drive inertial confinement fusion implosions is presented. The x-ray self emission of the target is measured with an x-ray framing camera. Optimized filtering limits the x-ray emission from the corona plasma, isolating a sharp intensity gradient very near the ablation surface. This enables one to measure the radius of the imploding shell with an accuracy better than 1 µm and to determine a 200-ps average velocity to better than 2%.

Time-resolved measurements of hot-electron equilibration dynamics in high-intensity laser interactions with thin-foil solid targets.

Time-resolved K(α) spectroscopy has been used to infer the hot-electron equilibration dynamics in high-intensity laser interactions with picosecond pulses and thin-foil solid targets. The measured K(α)-emission pulse width increases from ~3 to 6 ps for laser intensities from ~10(18) to 10(19) W/cm(2). Collisional energy-transfer model calculations suggest that hot electrons with mean energies from ~0.8 to 2 MeV are contained inside the target. The inferred mean hot-electron energies are broadly consistent with ponderomotive scaling over the relevant intensity range.

Phase-conjugate Fizeau interferometer.

We describe a phase-conjugate interferometer that consists of a partially transmitting conventional mirror placed in front of and in close proximity to a phase-conjugate mirror. The interferometer is self-referencing, compact, and insensitive to environmental disturbances, provides twice the sensitivity of conventional (nonphase-conjugate) interferometers, and produces a direct representation of an incident wave front. We have constructed such a device using internally self-pumped phase conjugation in barium titanate and have used the device to characterize the wave front produced by an aberrated optical system.