Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.

The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.

Novel rhesus macaque immunoglobulin germline genes identified by three sequencing approaches.

Introduction: Rhesus macaques have long been a focus of research for understanding immune responses to human pathogens due to their close phylogenetic relationship with humans. As rhesus macaque antibody germlines show high degrees of polymorphism, the spectrum of database-covered genes expressed in individual macaques remains to be determined.

Methods: Here, four rhesus macaques infected with SHIV became a study of interest because they developed broadly neutralizing antibodies against HIV-1.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Sources of HIV information and women's HIV knowledge in Southwest Sumba Indonesia: a cross-sectional study with mediation analysis.

Background: Despite multiple years of government HIV educational efforts, the growing trend of new cases among women in Indonesia runs parallel with their seemingly overall lack of comprehensive knowledge about HIV. A major prevention challenge for the Indonesian government lies in delivering HIV prevention education across the world's largest archipelago. This study investigates comprehensive HIV knowledge among reproductive-age women in Southwest Sumba, Indonesia, and the sources through which they report having learned about HIV along with potential mediators of the relationship between socioeconomic status (SES) and HIV knowledge.

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.

In silico analysis of human herpes virus-8 genome: a comparison of the K1, VR1, and VR2 regions for genotyping and global geographical distribution.

Investigations of the K1 gene revealed six main genotypes clustered according to geography. Here, the global distribution and HHV8 genotyping using the K1 gene and two hypervariable regions (VR1 and VR2) were evaluated. We searched GenBank for 6,889 HHV8-K1 genes via various keywords, selecting sequences longer than 730 bp.

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.

Investigation of integron classes 1, 2, and 3 among multi-drug resistant Staphylococcus aureus isolates in Iran: a multi-center study.

Background: Rising methicillin-resistant Staphylococcus aureus (MRSA) poses a global health threat, contributing to serious infections with high mortality rates. Integrons are recognized as significant genetic elements in disseminating multidrug-resistant (MDR) strains. This study focuses on assessing the prevalence of integron classes 1, 2, and 3 in S.

A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies.

Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.

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.

HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state.

HIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available.

DEVELOPING A PRACTICE-DRIVEN TAXONOMY OF IMPLEMENTATION STRATEGIES FOR HIV PREVENTION.

Background: Effective implementation of evidence-based HIV prevention interventions continues to be a challenge in the United States, and the field is increasingly turning to implementation science for solutions. As such, it is critical to expand the current implementation science vocabulary - and its taxonomy of implementation strategies - to increase its relevance and utility for front-line implementers.

Setting: Community-based health centers providing HIV prevention services in the Southeastern US.

Rapid and Safe Neutralization Assay for Circulating H5N1 Influenza Virus in Dairy Cows.

Rapid and safe neutralization assays are required for highly pathogenic avian influenza viruses, including a clade 2.3.4.

Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide.

Broadly neutralizing antibodies have been proposed as templates for HIV-1 vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1 fusion peptide, which comprises envelope (Env) residues 512-526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with substitutions to negatively charged amino acids at residue positions 517-520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV-1; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512-516 showing increased binding.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

Leveraging international stakeholders' experiences with oral PrEP costs to accelerate implementation of the monthly dapivirine vaginal ring: A qualitative study.

Background: Costing and financing systematic implementation are recognized barriers to human immunodeficiency virus (HIV) prevention. In the absence of empiric implementation and economic data, perspectives from international stakeholders involved in developing and supporting daily oral pre-exposure prophylaxis (PrEP) policy, and programs can provide critical insights for developing costed plans to support and accelerate the rollout of novel long-acting PrEP (LA-PrEP) methods, such as the monthly dapivirine vaginal ring (PrEP ring).

Methods: We interviewed stakeholders from purposively selected international organizations about anticipated PrEP-ring implementation costs, evidence gaps and key process steps for developing a costed rollout plan template (CRPT).

Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed.

Super broad and protective nanobodies against Sarbecoviruses including SARS-CoV-1 and the divergent SARS-CoV-2 subvariant KP.3.1.1.

The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.

Unlocking Therapeutic Potential: Enhanced shRNA Delivery with Tat Peptide in the Human Respiratory Syncytial Virus Treatment.

Purpose: This research investigated the development of short hairpin RNA (shRNA) molecules designed to target specific regions of the human respiratory syncytial virus (HRSV) M and F genes. The study aimed to assess the therapeutic potential of these shRNAs and evaluate the effectiveness of Tat peptide-mediated delivery in enhancing their functionality.

Methods: We acquired isolates from pediatric patients experiencing respiratory illness then cultured in HEp-2 cells.

Characterizing people who inject drugs with no history of opioid agonist therapy uptake in Iran: Results from a national bio-behavioural surveillance survey in 2020.

Injection drug use is the primary driver of the human immunodeficiency virus HIV epidemic in Iran. We characterized people who inject drugs (PWID) living in Iran who had never received opioid agonist therapy (OAT) and examined barriers to OAT uptake. We recruited 2,684 PWID with a history of drug injection in the previous 12 months using a respondent-driven sampling approach from 11 geographically dispersed cities in Iran.

Environmental factors and chronic kidney disease: a case-control study.

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders causing abnormal renal function and progressive decline in the glomerular filtration rate (GFR). This study aimed to investigate the associations of several Environmental factors with CKD in the Iranian population. This is the second phase of a hospital-based case-control study, which was conducted on 700 participants (350 CKD cases and 350 controls, age and gender frequency matched).

A Transcriptional Signature of Induced Neurons Differentiates Virologically Suppressed People Living With HIV from People Without HIV.

Neurocognitive impairment is a prevalent and important co-morbidity in virologically suppressed people living with HIV (PLWH), yet the underlying mechanisms remain elusive and treatments lacking. Here, we explored for the first time, use of participant-derived directly induced neurons (iNs) to model neuronal biology and injury in PLWH. iNs retain age- and disease-related features of the donors, providing unique opportunities to reveal novel aspects of neurological disorders.