Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Background: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.

Research Question: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?

Study Design And Methods: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473).

Greater activation of peripheral T follicular helper cells following high dose influenza vaccine in older adults forecasts seroconversion.

Background: Influenza related morbidity and mortality disproportionately impacts older adults. The serologic response to vaccine is diminished in older adults; however, high dose inactivated influenza vaccine (HD IIV) has shown improved rates of seroconversion compared to standard dose (SD IIV). We hypothesize this may be due to the superior ability of high dose vaccine to activate T follicular helper (Tfh) cells and provide B cell dependent T cell help.

H7N9 influenza virus neutralizing antibodies that possess few somatic mutations.

Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors.

Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival.

Regulatory T cells (Tregs) are a subset of CD4(+) T cells that are characterized by the expression of CD25 and Foxp3 and are capable of suppressing alloimmune responses. We assessed whether high frequencies of circulating skin or gut tissue-specific Tregs at engraftment could predict acute graft-vs-host disease (aGVHD) incidence and survival in a cohort of hematopoietic cell transplant (HCT) recipients. Tregs were analyzed at engraftment in 74 patients receiving HCT.

Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity.

Chronic inflammation and decreased frequency of regulatory T cells (Tregs) in visceral adipose tissue contribute to the propagation of insulin resistance to diabetes mellitus. We tested the hypothesis that new-onset posttransplantation diabetes mellitus (PTDM) is associated with measurable changes in Treg subsets after allogeneic hematopoietic stem cell transplantation (HSCT). PTDM before day 100 and Treg phenotype at engraftment were determined in 36 HSCT recipients without preceding history of diabetes mellitus.

Identification of potential human respiratory syncytial virus and metapneumovirus T cell epitopes using computational prediction and MHC binding assays.

Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are two of the most common causes of serious viral lower respiratory tract illness in humans. CD8+ T cells have been shown to be important in animal models and human clinical studies for the clearance of viral infection, and they may contribute in part to protection against severe disease during reinfections. Precise enumeration and accurate phenotyping of RSV- or MPV-specific CD8+ T cells in humans is currently limited by the relatively small number of T cell epitopes that have been mapped with accompanying identification of MHC restriction patterns.

Antibodies recognizing protective pertussis toxin epitopes are preferentially elicited by natural infection versus acellular immunization.

Despite more than 50 years of vaccination, disease caused by the bacterium Bordetella pertussis persists, with rates increasing in industrialized countries over the past decade. This rise may be attributed to several factors, including increased surveillance, emergence of vaccine escape variants, waning immunity in adults, and the introduction of acellular subunit vaccines, which include chemically detoxified pertussis toxin (PTd). Two potently protective epitopes on pertussis toxin (PTx) are recognized by the monoclonal antibodies 1B7 and 11E6, which inhibit catalytic and cell-binding activities, respectively.

Cellular immune responses to diluted and undiluted aventis pasteur smallpox vaccine.

Background: Recent primary vaccine trials of diluted Aventis Pasteur smallpox vaccine (APSV) demonstrated that immunization "take" rates, defined by the presence of a vesicle or pustule ("take") at the inoculation site 6-11 days after immunization, did not differ between the dilution groups. To our knowledge, there have been no studies that examine the cellular immune response or that distinguish CD4(+) T cell responses from CD8(+) T cell responses after primary immunization with varying dilutions of APSV.

Methods: In the present study, we examined the cellular immune response in vaccinia-naive healthy adults (n=91) receiving inoculations with an undiluted or diluted (1:5 and 1:10) suspension of the APSV, using an intracellular cytokine staining assay.

Differential regulation of granzyme and perforin in effector and memory T cells following smallpox immunization.

Primary immunization of healthy adults with vaccinia virus induces a local vesicle or "take" in the majority of vaccinees that previously has been shown to correlate with protection against smallpox. However, the immunologic mechanisms underlying this protective response in humans are not well characterized. We have studied human CD8+ T cells for the expression patterns of phenotypic markers and cytolytic effector molecules before and after primary smallpox immunization using nine-color polychromatic flow cytometry.

Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial.

Context: Additional smallpox vaccine doses are needed to augment current US national stockpile. Aventis Pasteur smallpox vaccine (APSV), initially manufactured in the 1950s from the New York Board of Health vaccinia strain in a frozen preparation, appears as effective as lyophilized vaccine but the effectiveness of diluted doses of APSV is unclear.

Objective: To compare the vaccination success rate and the reaction profile of various APSV dilutions.

Adverse events after smallpox immunizations are associated with alterations in systemic cytokine levels.

The immunization of healthy adults with vaccinia virus (VV) induces a protective response against smallpox in most individuals but is also reactogenic in a significant number of vaccinees. The immunological mechanisms underlying the protective response or adverse events in humans are not well defined. Although cytokines contribute to antiviral immunity and, in some cases, cause systemic adverse effects, their role in the human response to VV is unknown.

Role of complement in neutralization of respiratory syncytial virus.

Serum neutralizing antibody titers to respiratory syncytial virus (RSV) are higher when assayed with guinea pig complement. A number of different mechanisms have been suggested for enhancement of neutralization by complement. The most straightforward is that complement-antibody complexes present a greater steric hindrance to viral entry than with antibody alone.