Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial.

Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.

The effect of the mechanodynamic lung environment on fibroblast phenotype via the Flexcell.

The lung is a highly mechanical organ as it is exposed to approximately 10 strain cycles, (where strain is the length change of tissue structure per unit initial length), with an approximately 4% amplitude change during quiet tidal breathing or 10 strain cycles at a 25% amplitude during heavy exercises, sighs, and deep inspirations. These mechanical indices have been reported to become aberrant in lung diseases such as acute respiratory distress syndrome (ARDS), pulmonary hypertension, bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), and asthma. Through recent innovations, various in vitro systems/bioreactors used to mimic the lung's mechanical strain have been developed.

Reverse development of vaccines against antimicrobial-resistant pathogens.

Vaccine R&D is typically a lengthy process taking >10 years. However, vaccines still fail in clinical development because of unreliable animal models or absent immunological correlates of protection. Without a correlate of protection, phase-1 and -2 studies of safety and immunogenicity can fail to predict phase-3 efficacy.

In vitro co-culture studies and the crucial role of fibroblast-immune cell crosstalk in IPF pathogenesis.

IPF is a fatal lung disease characterized by intensive remodeling of lung tissue leading to respiratory failure. The remodeling in IPF lungs is largely characterized by uncontrolled fibrosis. Fibroblasts and their contractile phenotype the myofibroblast are the main cell types responsible for typical wound healing responses, however in IPF, these responses are aberrant and result in the overactivation of fibroblasts which contributes to the inelasticity of the lung leading to a decrease in lung function.

3D in vitro hydrogel models to study the human lung extracellular matrix and fibroblast function.

The pulmonary extracellular matrix (ECM) is a macromolecular structure that provides mechanical support, stability and elastic recoil for different pulmonary cells including the lung fibroblasts. The ECM plays an important role in lung development, remodeling, repair, and the maintenance of tissue homeostasis. Biomechanical and biochemical signals produced by the ECM regulate the phenotype and function of various cells including fibroblasts in the lungs.

Epithelial-fibroblast interactions in IPF: Lessons from in vitro co-culture studies.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with excessive extracellular matrix (ECM) deposition leading to buildup of scar tissue (fibrosis) and remodeling in the lungs. The activated and differentiated (myo)fibroblasts are one of the main sources of tissue remodeling in IPF and a crucial mechanism known to contribute to this feature is an aberrant crosstalk between pulmonary fibroblasts and the abnormal or injured pulmonary epithelium. This epithelial-fibroblast interaction mimics the temporal, spatial and cell-type specific crosstalk between the endoderm and mesoderm in the so-called epithelial-mesenchymal trophic unit (EMTU) during lung development that is proposed to be activated in healthy lung repair and dysregulated in various lung diseases including IPF.

Synthesis of plant-based, self-adjuvanted, dual antigen specific to Mycobacterium tuberculosis as a novel tuberculosis subunit vaccine that elicits immunogenicity in rabbit.

Objectives: The only approved vaccine, Bacillus Calmette Guérin (BCG) used in global tuberculosis (TB) immunization programmes has been very effective in childhood TB but not in adult pulmonary and latent TB. Moreover, the emergence of multi-drug resistance-TB cases demands either to increase efficiency of BCG or replace it with the one with improved efficacy.

Results: A novel combination of two most effective secreted protein antigens specific for Mycobacterium tuberculosis (Mtb), ESAT-6 and MPT-64 (but not present in BCG strains) fused with a cholera toxin B subunit (CTB) and tagged with 6xHis was expressed for the first time in Escherichia coli as well as in transgenic cucumber plants developed using Agrobacterium tumefaciens-mediated transformation.

Understanding fibroblast-immune cell interactions co-culture models and their role in asthma pathogenesis.

Asthma is a chronic lung disease involving airway inflammation and fibrosis. Fibroblasts are the main effector cells important for lung tissue production which becomes abnormal in asthmatics and is one of the main contributors to airway fibrosis. Although fibroblasts were traditionally viewed solely as structural cells, they have been discovered to be highly active, and involved in lung inflammatory and fibrotic processes in asthma.

Recent advances and future perspectives on carbohydrate-based cancer vaccines and therapeutics.

Carbohydrates are abundantly expressed on the surface of both eukaryotic and prokaryotic cells, often as post translational modifications of proteins. Glycoproteins are recognized by the immune system and can trigger both innate and humoral responses. This feature has been harnessed to generate vaccines against polysaccharide-encapsulated bacteria such as Streptococcus pneumoniae, Hemophilus influenzae type b and Neisseria meningitidis.

TMQuery: a database of precomputed template modeling scores for assessment of protein structural similarity.

Summary: Comparisons of protein structures are critical for developing novel protein designs, annotating protein functions and predicting protein structure. The template modeling score (TM-score) is a widely used but computationally expensive measure of protein similarity that is applicable to a wide variety of structural biology problems. We introduce TMQuery-a continuously updated database containing over eight billion pre-computed TM-score values for every pair of proteins in the Protein Data Bank, allowing researchers to quickly query and download TM-scores via a web interface.

Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies.

is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures.

Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection.

We investigated serological responses following a SARS-CoV-2 outbreak in spring 2020 on a US Marine recruit training base. 147 participants that were isolated during an outbreak of respiratory illness were enrolled in this study, with visits approximately 6 and 10 weeks post-outbreak (PO). This cohort is comprised of young healthy adults, ages 18-26, with a high rate of asymptomatic infection or mild symptoms, and therefore differs from previously reported longitudinal studies on humoral responses to SARS-CoV-2, which often focus on more diverse age populations and worse clinical presentation.

Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

Background: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa.

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses.

Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based immunoassay strategies for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2 and the endemic seasonal human coronaviruses (HCoV), enabling high throughout measurement of pre-existing cross-reactive antibodies.

SARS-CoV-2 Infections and Serologic Responses Among Military Personnel Deployed on the USNS COMFORT to New York City During the COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) presents a unique challenge to United States Navy hospital ships. The aim of this study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among US Navy personnel deployed on the USNS COMFORT to augment the inpatient health care capacity in New York City.

Methods: This was a cross-sectional study conducted on USNS COMFORT crewmembers returning to Norfolk, Virginia, following deployment.

A finite element analysis to study the stress distribution on distal implants in an all-on-four situation in atrophic maxilla as affected by the tilt of the implants and varying cantilever lengths.

Aim: The aim of this work was to evaluate stress distribution on implants in All-on-Four situation with varying distal implant angulations (30°,40°,45°) and varying cantilever lengths (4 mm, 8 mm, 12 mm, 16 mm) in atrophic maxilla using finite element analysis.

Setting And Design: A study, finite element analysis.

Materials And Methodology: Three-dimensional finite element model of an edentulous maxilla restored with a prosthesis supported by four implants was reconstructed to carry out the analysis.

Vaccinology in the post-COVID-19 era.

The COVID-19 pandemic is a shocking reminder of how our world would look in the absence of vaccination. Fortunately, new technologies, the pace of understanding new and existing pathogens, and the increased knowledge of the immune system allow us today to develop vaccines at an unprecedented speed. Some of the vaccine technologies that are fast-tracked by the urgency of COVID-19 may also be the answer for other health priorities, such as antimicrobial resistance, chronic infections, and cancer, that the post-COVID-19 world will urgently need to face.

A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and antibody cross reactions.

Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we developed and applied a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human betacoronaviruses, HCoV-HKU1 and HCoV-OC43, that enables measurement of off-target pre-existing cross-reactive antibodies. The MMIA performances characteristics are: 98% sensitive and 100% specific for human subject samples collected as early as 10 days from symptom onset.

A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and controls for pre-existing seasonal human coronavirus antibody cross-reactivity.

With growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utilizing serum samples from non-human primate SARS-CoV-2 infection models, an archived human sera bank and subjects enrolled at five U.S.

Esthetic Rehabilitation Using Magnet-Retained Cheek Plumper Prosthesis.

. Prosthetic rehabilitation of a completely edentulous patient is no more confined to replacement of missing teeth. Long span of edentulism and ageing leads to loss of support of the facial musculature, which is of great concern in treating completely edentulous patients.

Inductively coupled plasma nanosilica based growth method for enhanced biomass production in marine diatom algae.

This work reports a novel solution-based method to trigger the growth of diatoms for enhanced biomass production, which can efficiently stimulate their applications in nutraceuticals, aquaculture and wastewater remediation. The optimization for the growth of three marine diatoms species was performed using inductively coupled plasma (ICP) synthesized nanosilica which can be a cost-effective and productive method for biomass production. The exponential growth phase was achieved in 14 days with high biomass productivity compared to F/2-Si Media [Chaetoceros sp.

Correction: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

[This corrects the article DOI: 10.1371/journal.ppat.

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines.

Background: HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses.

Methods And Findings: A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and with bivalent subtype C gp120/MF59 at months 3, 6, and 12.

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial.

Background: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost.

Methods: RV306 is a double-blind, placebo-controlled, randomised clinical trial done at three clinical sites in Thailand.