Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate

Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp140(94UG018)). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp140(94UG018). Our results provide a rationale for the design and evaluation of immunogens and the clade A gp140(94UG018) shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity

International Network for Comparison of HIV Neutralization Assays: The NeutNet Report II

BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation

The epidemiology and natural history of genital herpes simplex virus (HSV) infection

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Pandemic, Infodemic, and People’s Resilience in India: Viewpoint

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused widespread fear and stress. The pandemic has affected everyone, everywhere, and created systemic inequities, leaving no one behind. In India alone, more than 34,094,373 confirmed COVID-19 cases and 452,454 related deaths have been reported as of October 19, 2021. Around May 2021, the daily number of new COVID-19 cases crossed the 400,000 mark, seriously hampering the health care system. Despite the devastating situation, the public response was seen through their efforts to come forward with innovative ideas for potential ways to combat the pandemic, for instance, dealing with the shortage of oxygen cylinders and hospital bed availability. With increasing COVID-19 vaccination rates since September 2021, along with the diminishing number of daily new cases, the country is conducting preventive and preparatory measures for the third wave. In this article, we propose the pivotal role of public participation and digital solutions to re-establish our society and describe how Sustainable Development Goals (SDGs) can support eHealth initiatives and mitigate infodemics to tackle a postpandemic situation. This viewpoint reflects that the COVID-19 pandemic has featured a need to bring together research findings across disciplines, build greater coherence within the field, and be a driving force for multi-sectoral, cross-disciplinary collaboration. The article also highlights the various needs to develop digital solutions that can be applied to pandemic situations and be reprocessed to focus on other SDGs. Promoting the use of digital health care solutions to implement preventive measures can be enhanced by public empowerment and engagement. Wearable technologies can be efficiently used for remote monitoring or home-based care for patients with chronic conditions. Furthermore, the development and implementation of informational tools can aid the improvement of well-being and dissolve panic-ridden behaviors contributing toward infodemics. Thus, a call to action for an observatory of digital health initiatives on COVID-19 is required to share the main conclusions and lessons learned in terms of resilience, crisis mitigation, and preparedness

Radical Transformation of Universities to Prepare the Next Generation of Climate Champions

© UNESCO IBE, 2021 | DOI: 10.1163/9789004471818_005 This is an open access chapter distributed under the terms of the CC BY 4.0 LicensePeer ReviewedThe threat and reality of climate change must be acted upon individually and collectively. Universities have a decisive role to play in this regard – by creating the capacity in all its academic activities to lead in taking on the challenge and by graduating students with the capacity to solve the problems that the climate change situation poses. To take on these roles, universities must accept a “radical transformation”. Radical transformation is a process that requires two integrated activities: radical thinking and transformative action. We propose that it is radical to think of universities as microcosms of society; that is, universities face the same need as everyone else to find ways to mitigate and adapt to climate change. We also propose that it is transformative for universities to inspire and be agents of change for the world: by creatively developing strategies to mitigate and adapt to climate change, universities can become global leaders in demonstrating workable solutions capable of being broadly diffused and scaled up. We present a set of design aspirations that can help universities undergo a radical transformation and thereby make headway in addressing the climate crisis

Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. RESULTS: It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies

Circulatory Serum Krebs von Den Lungen-6 and Surfactant Protein-D Concentrations Predict Interstitial Lung Disease Progression and Mortality

There is a need for biomarkers to predict outcomes, including mortality, in interstitial lung disease (ILD). Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are associated with lung damage and fibrosis in all ILDs and are related to important clinical outcomes. Though these two biomarkers have been associated with ILD outcomes, there are no studies that have evaluated their predictive potential in combination. This study aims to determine whether KL-6 and SP-D are linked to poor disease outcomes and mortality. Additionally, we plan to examine whether changes in KL-6 and SP-D concentrations correspond with changes in lung function and whether serial measurements improve their predictive potential to identify disease progression and mortality. Forty-four patients with ILD participated in a prospective 6-month longitudinal observational study. ILD patients who succumbed had the highest KL-6 levels (3990.4 U/mL (3490.0–4467.6)) and highest SP-D levels (256.1 ng/mL (217.9–260.0)), followed by those who deteriorated: KL-6 levels 1357.0 U/mL (822.6–1543.4) and SP-D levels 191.2 ng/mL (152.8–210.5). The generalized linear model (GLM) analysis demonstrated that changes in forced vital capacity (FVC), diffusing capacity of lungs for carbon monoxide (DLCO), forced expiratory volume in 1 s (FEV1), and partial pressure of arterial oxygen (PaO2) were correlated to changes in KL6 (p = 0.016, 0.014, 0.027, 0.047) and SP-D (p = 0.008, 0.012, 0.046, 0.020), respectively. KL-6 (odds ratio (OR): 2.87 (1.06–7.79)) and SPD (OR: 1.76 (1.05–2.97)) were independent predictors of disease progression, and KL-6 (hazard ratio (HR): 3.70 (1.46–9.41)) and SPD (HR: 2.58 (1.01–6.59)) were independent predictors of death by Cox regression analysis. Combined biomarkers (KL6 + SPD + CT + FVC) had the strongest ability to predict disease progression (AUC: 0.797) and death (AUC: 0.961), on ROC analysis. Elevated KL-6 and SPD levels are vital biomarkers for predicting the severity, progression, and outcomes of ILD. High baseline levels or an increase in levels over a six-month follow-up despite treatment indicate a poor prognosis. Combining KL6 and SPD with conventional measures yields a more potent prognostic indicator. Clinical studies are needed to test additional interventions, and future research will determine if this combined biomarker benefits different ethnicities globally