Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine.

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22).

Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

Background: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from infection in a region where this organism is endemic is unclear.

Methods: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season.

Evaluation of the implementation of a community health worker-led COVID-19 contact tracing intervention in Chiapas, Mexico, from March 2020 to December 2021.

Background: Mexico is one of the countries with the greatest excess death due to COVID-19. Chiapas, the poorest state in the country, has been particularly affected. Faced with an exacerbated shortage of health professionals, medical supplies, and infrastructure to respond to the pandemic, the non-governmental organization Compañeros En Salud (CES) implemented a COVID-19 infection prevention and control program to limit the impact of the pandemic in the region.

Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.

Background: Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available.

An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem.

A comprehensive and healthcare equity promoting response by a civil society-public partnership to COVID-19 in Chiapas, Mexico.

Following the first COVID-19 case in Chiapas, Mexico in March 2020, the non-governmental organisation Compañeros En Salud (CES) and the state's Ministry of Health (MOH) decided to join forces to respond to the global pandemic. The collaboration was built over 8 years of partnership to bring healthcare to underserved populations in the Sierra Madre region. The response consisted of a comprehensive SARS-CoV-2 infection prevention and control programme, which included prevention through communication campaigns to combat misinformation and stigma related to COVID-19, contact tracing of suspected and confirmed COVID-19 cases and their contacts, outpatient and inpatient care for patients with respiratory symptoms, and CES-MOH collaboration on anti-COVID-19 immunisation campaigns.

Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

Background: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults.

Methods: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA.

Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial.

Background: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two parts of a three-part clinical trial, the antimalarial monoclonal antibody CIS43LS conferred high protection against parasitaemia at doses of 20 mg/kg or 40 mg/kg administered intravenously followed by controlled human malaria infection. The ability of CIS43LS to confer protection at lower doses or by the subcutaneous route is unknown.

Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria.

Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed.

Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight.

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial.

Background: Advances in therapeutic drugs have increased life-expectancies for HIV-infected individuals, but the need for an effective vaccine remains. We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV-negative adults.

Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial.

Background: Western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses are mosquito-borne pathogens classified as potential biological warfare agents for which there are currently no approved human vaccines or therapies. We aimed to evaluate the safety, tolerability, and immunogenicity of an investigational trivalent virus-like particle (VLP) vaccine, western, eastern, and Venezuelan equine encephalitis (WEVEE) VLP, composed of WEEV, EEEV, and VEEV VLPs.

Methods: The WEVEE VLP vaccine was evaluated in a phase 1, randomised, open-label, dose-escalation trial at the Hope Clinic of the Emory Vaccine Center at Emory University, Atlanta, GA, USA.

Perspectives on high-quality interpersonal care among people obtaining abortions in Argentina.

Introduction: Little is known about how people who have abortions describe high-quality interpersonal care in Argentina. This qualitative study aimed to understand preferences and priorities in their interactions with providers.

Study Design: We conducted 24 in-depth interviews with people who obtained abortions at a comprehensive reproductive health clinic or with support from a feminist accompaniment group in Buenos Aires and Neuquén, Argentina.

Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.

Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968.

A Monoclonal Antibody for Malaria Prevention.

Background: Additional interventions are needed to reduce the morbidity and mortality caused by malaria.

Methods: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria.

Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study.

Background: mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. Here we present expedited data from VRC 608, a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity.

Methods: In this phase 1, dose-escalation study (VRC 608), conducted at the US National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA), healthy adults aged 18-60 years were sequentially enrolled into three mAb114 dose groups of 5 mg/kg, 25 mg/kg, and 50 mg/kg.

Centenarians and their hearts: A prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up.

Background: Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data.

Methods: We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.

Comorbidity and intervention in octogenarians with severe symptomatic aortic stenosis.

Background: The benefit from intervention in elderly patients with symptomatic severe aortic stenosis (AS) and high comorbidity is unknown. Our aims were to establish the correlation between the Charlson comorbidity index and the prognosis of octogenarians with symptomatic sever AS and to identify patients who might not benefit from intervention.

Methods: We used the data from PEGASO (Pronóstico de la Estenosis Grave Aórtica Sintomática del Octogenario--Prognosis of symptomatic severe aortic stenosis in octogenarians), a prospective registry that included consecutively 928 patients aged ≥ 80 years with severe symptomatic AS.

Transient infrared spectroscopy: a new approach to investigate valence tautomerism.

In this work we present, to our knowledge for the first time, the results of a transient infrared spectroscopic study of the photoinduced valence tautomerism process in cobalt-dioxolene complexes with sub-picosecond time resolution. The molecular systems investigated were [Co(tpa)(diox)]PF(6) (1) and [Co(Me(3)tpa)(diox)]PF(6) (2), where diox = 3,5-di-tert-butyl-1,2-dioxolene; tpa = tris(2-pyridylmethyl)amine and Me(3)tpa its 6-methylated analogue. Complex (1) is present in solution as ls-Co(III)(catecholate) (1-CAT), while (2) as hs-Co(II)(semiquinonate) (2-SQ).

General overview of the Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations.

The Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held in Madrid on the 6th and 7th of May 2010. Gathering for the seventh consecutive year the most relevant researchers and opinion leaders on cardiovascular cell therapy, it has become the most important worldwide event on this field. A comprehensive review of the last developments on cell therapy, surgery for heart failure and tissue engineering was made, and the results of three clinical trials were reported.

Stem cell therapy in chronic ischemic heart dysfunction with and without viability.

A growing number of clinical trials are evaluating the effects of stem cell therapy in patients with chronic ischemic heart dysfunction. As most of the clinical trials included a limited and different number of patients, various stem cell sources and several delivery approaches, results vary substantially between these studies. We analyse whether the assessment of myocardial viability may be important when evaluating effects of stem cell transplantation on parameters of left ventricular remodeling.

General overview of the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations.

Being one of the main stem cell therapy meetings of the year, the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held on April 23rd-24th, 2009, at the Auditorium of the High Council of Scientific Research of Spain (CSIC) in Madrid. Gathering the most prestigious basic researchers and clinical experts in the field of cardiovascular regenerative medicine, the aim of the meeting was to discuss the available evidence and the recent contributions from preclinical investigators, cardiologists, and cardiac surgeons in a participative translational fashion. The role of young "clinician scientists" was reinforced with a special poster session and three awards.