Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum.

Background: Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge.

Antibody in Lymphocyte Supernatant (ALS) responses after oral vaccination with live Shigella sonnei vaccine candidates WRSs2 and WRSs3 and correlation with serum antibodies, ASCs, fecal IgA and shedding.

The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner.

Effect of Concomitant Antibiotic and Vaccine Administration on Serologic Responses to Rotavirus Vaccine.

Data from 1174 infants enrolled in a previous rotavirus vaccine study were analyzed to determine the effect of antibiotic exposure (from 14 days before to 7 days after vaccination) on rotavirus serum immunoglobulin A (IgA) responses. Serum IgA responses 1 month after the completion of vaccination were similar among antibiotic-exposed and nonexposed infants.

Safety and Differential Antibody and T-Cell Responses to the Sporozoite Malaria Vaccine, PfSPZ Vaccine, by Age in Tanzanian Adults, Adolescents, Children, and Infants.

In 2016, there were more cases and deaths caused by malaria globally than in 2015. An effective vaccine would be an ideal additional tool for reducing malaria's impact. Sanaria PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved (Pf) sporozoites (SPZ) has been well tolerated and safe in malaria-naïve and experienced adults in the United States and Mali and protective against controlled human malaria infection with Pf in the United States and field transmission of Pf in Mali, but had not been assessed in younger age groups.

A Phase 1 dose escalating study of double mutant heat-labile toxin LTR192G/L211A (dmLT) from Enterotoxigenic Escherichia coli (ETEC) by sublingual or oral immunization.

Background: The public health burden of Enterotoxigenic Escherichia coli (ETEC) is high but no vaccine is specifically approved to prevent ETEC infections.

Methods: We performed a Phase 1, dose escalation study (1-50 µg) evaluating the sublingual (SL) delivery of the double mutant heat-labile toxin LTR192G/L211A (dmLT) in 80 healthy adult volunteers. The primary objective was safety and the secondary was the immunogenicity of the dmLT.

A Phase I trial to evaluate the safety and immunogenicity of WRSs2 and WRSs3; two live oral candidate vaccines against Shigella sonnei.

Effective vaccines are needed to combat diarrheal diseases due to Shigella. Two live oral S. sonnei vaccine candidates, WRSs2 and WRSs3, attenuated principally by the lack of spreading ability, as well as the loss of enterotoxin and acyl transferase genes, were tested for safety and immunogenicity.

Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE).

ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

Methods: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.

Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study).

Rationale: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure.

Objective: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy.

Methods And Results: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial.

Background: Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM).

Objectives: The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM.

Methods: Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio.

Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax.

Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB) containing 3 distinct mutations in the major histocompatibility complex class II binding site was combined with an alum adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax. Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a first-in-human open-label dose escalation study of parenteral doses of STEBVax ranging from 0.

Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.

Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.

Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules.

Background And Objectives: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone.

Methods: Randomized, multicenter, open-label study.

Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients.

Background: The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial.

Objectives: This study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects.

Methods: Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older.

Acute heart failure in the elderly: differences in clinical characteristics, outcomes, and prognostic factors in the VERITAS Study.

Background: Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly.

Methods And Results: We analyzed the clinical and laboratory characteristics and the outcomes of 1,347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age of 72 years.

The iterative proportional fitting algorithm for adjusted agreement in a non-inferiority diagnostic clinical trial.

In this paper, we describe a method of comparing agreement between two diagnostic contingency tables after adjustment to more clinically relevant marginal distributions using the iterative proportional fitting algorithm. When the categories of a contingency table represent mild, moderate, and severe outcomes, the majority of patients often are in the mild category. Because it is often of more interest to evaluate agreement when patients are uniformly distributed among categories, we present the primary results of two clinical trials with adjustment to this structure.

Knowledge and beliefs regarding oral health among pregnant women.

Background: Racial or ethnic and economic disparities exist in terms of oral diseases among pregnant women and children. The authors hypothesized that women of a racial or ethnic minority have less oral health knowledge than do women not of a racial or ethnic minority. Therefore, the authors conducted a study to assess and compare maternal oral health knowledge and beliefs and to determine if maternal race and ethnicity or other maternal factors contributed to women's knowledge or beliefs.