Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening.

Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.

The clinical indexes and immunological status of HIV/AIDS patients undergoing different highly active antiretroviral treatments.

Objective: This study aims to investigate the differences of clinical indices in HIV patients between three different first-line antiretroviral treatment strategies in Yunnan Province, China. Furthermore, the hematologic system, liver function, kidney function, blood lipid levels of HIV patients and its association with CD4+ count, CD8+ count, CD4/CD8 ratio and antiretroviral treatment were also assessed.

Methods: This retrospective cohort study included 81 participants who underwent highly active antiretroviral treatment from September 2009 to September 2019.

Conference 2024: Building an innovative scientific research ecosystem for microbiome and One Health.

The Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals.

Unveiling neuroimmunology profile of immunological non-responders in HIV: a multimodal MRI approach.

Background: People living with HIV (PLWH), especially immunological non-responders (INRs), may experience adverse neurologic events. However, the extent of neurological impairment in INRs remains uncertain. This study evaluates brain structure and function, immune dysregulation, and peripheral immunomarkers in INRs and immunological responders (IRs) among PLWH, classified according to immunological response criteria, within a clinical research setting.

SLAMF7 defines subsets of human effector CD8 T cells.

Long-term control of viral replication relies on the efficient differentiation of memory T cells into effector T cells during secondary immune responses. Recent findings have identified T cell precursors for both memory and exhausted T cells, suggesting the existence of progenitor-like effector T cells. These cells can persist without antigenic challenge but expand and acquire effector functions upon recall immune responses.

Memory stem CD8T cells in HIV/Mtb mono- and co-infection: characteristics, implications, and clinical significance.

Human immunodeficiency Virus (HIV) and () co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/ co-infection is complex and challenging. CD8T cells play a pivotal role in the adaptive immune response to both HIV and .

Efficacy of transcutaneous electrical acupoint stimulation for immunological non-responder in HIV/AIDS combined with amphetamine abuse: study protocol for a randomized controlled trial.

Background: Amphetamine-type stimulant (ATS) abuse is strongly associated with an elevated risk of HIV infection and transmission. Antiretroviral therapy (ART) serves as the primary approach for managing HIV infection and AIDS progression. However, ATS abuse diminishes the efficacy of ART in HIV/AIDS patients, amplifying the vulnerability to immunological non-response (INR) and ultimately increasing the incidence rate and mortality of opportunistic infections.

Humoral response 24 months after the first COVID-19 vaccination in people with HIV with and without diabetes.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database.

Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.

Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included.

Blocking Deoxycytidine Kinase in Activated Lymphocytes Depletes Deoxycytidine Triphosphate Pools and Alters Cell Cycle Kinetics to Yield Less Disease in a Mouse Multiple Sclerosis Model.

Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides.

Platelet-Neutrophil aggregate formation induces NLRP3 inflammasome activation in VITT.

Background: Although rare, vaccine-induced thrombotic thrombocytopenia (VITT) following adenoviral vector COVID-19 vaccination is a concerning and often severe adverse effect of vaccination. The generation of high anti-platelet factor 4 (PF4) antibody titers, promotes the formation of immune complexes capable of activating platelets and neutrophils through FcγRIIa.

Objective: Given that Platelet-leukocyte aggregate (PLA) formation and inflammasome activation are common features of thromboinflammatory diseases, we aimed to evaluate if these are also features of VITT.

Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19.

Recommendations for the optimal introduction of novel antibiotics to treat uncomplicated gonorrhoea in the face of increasing antimicrobial resistance: a case study with zoliflodacin.

New, first-in-class oral antibiotics like zoliflodacin, developed in a public-private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase.

Nutritionally acquired immunodeficiency must be addressed with the same urgency as HIV to end tuberculosis.

Tuberculosis (TB) is the leading infectious killer worldwide, with 10.6 million cases and 1.6 million deaths in 2021 alone.

Modulation of antigen delivery and lymph node activation in nonhuman primates by saponin adjuvant saponin/monophosphoryl lipid A nanoparticle.

Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in nonhuman primates (NHPs) comparing the most common clinical adjuvant aluminum hydroxide (alum) with saponin/monophosphoryl lipid A nanoparticles (SMNP), an immune-stimulating complex-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum, including 7-fold higher peak antigen-specific germinal center B-cell responses, 18-fold higher autologous neutralizing antibody titers, and higher levels of antigen-specific plasma and memory B cells.

Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa: A randomized crossover phase 2a/2b trial.

COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo.

Dysbiosis of gut microbiota in COVID-19 is associated with intestinal DNA phage dynamics of lysogenic and lytic infection.

This study compared intestinal DNA phage dynamics and gut microbiota changes observed at the onset of coronavirus disease 2019 (COVID-19). The study participants included 19 healthy individuals and 19 patients with severe acute respiratory syndrome coronavirus 2 infection. Significant differences were observed in the diversity of the intestinal DNA virome after the onset of COVID-19 compared with that in healthy individuals.

SARS-CoV-2 Infection Risk by Vaccine Doses and Prior Infections Over 24 Months: ProHEpiC-19 Longitudinal Study.

Background: As the vaccination campaign against COVID-19 progresses, it becomes crucial to comprehend the lasting effects of vaccination on safeguarding against new infections or reinfections.

Objective: This study aimed to assess the risk of new SARS-CoV-2 infections based on the number of vaccine doses, prior infections, and other clinical characteristics.

Methods: We defined a cohort of 800 health care workers in a 24-month study (March 2020 to December 2022) in northern Barcelona to determine new infections by SARS-CoV-2.

PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial.

Introduction: Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac () () (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.

A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates.

The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates.

Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab).

Executive summary: Clinical practice guidelines on the management of resistant tuberculosis of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) have developed together Clinical Practice Guidelines (GPC) on the management of people affected by tuberculosis (TB) resistant to drugs with activity against Mycobacterium tuberculosis. These clinical practice guidelines include the latest updates of the SEPAR regulations for the diagnosis and treatment of drug-resistant TB from 2017 to 2020 as the starting point. The methodology included asking relevant clinical questions based on PICO methodology, a literature search focusing on each question, and a systematic and comprehensive evaluation of the evidence, with a summary of this evidence for each question.

Screening for cryptococcal antigenemia and meningeal cryptococcosis, genetic characterization of Cryptococcus neoformans in asymptomatic patients with advanced HIV disease in Kinshasa, Democratic Republic of Congo.

We evaluated the prevalence of serum and meningeal cryptococcosis in asymptomatic outpatients with advanced HIV disease (CD4 < 200 cells/mm3) in a cross-sectional screening context in Kinshasa clinics (DRC). Lumbar puncture (LP) was performed in patients with positive serum cryptococcal antigen (CrAg) test, and Cryptococcus spp. isolated from cerebrospinal fluid (CSF) were identified by MALDI-TOF-MS, and characterized using serotyping-PCR, ITS-sequencing and multilocus sequence typing (MLST).