Synthetic Neoglycoconjugates of Hepta- and Nonamannoside Ligands for Eliciting Oligomannose-Specific HIV-1-Neutralizing Antibodies.

Oligomannose-type glycans on the spike protein of HIV-1 constitute relevant epitopes to elicit broadly neutralizing antibodies (bnAbs). Herein we describe an improved synthesis of α- and β-linked hepta- and nonamannosyl ligands that were subsequently converted into BSA and CRM neoglycoconjugates. We assembled the ligands from anomeric 3-azidopropyl spacer glycosides from select 3-O-protected thiocresyl mannoside donors.

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies.

The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope.

HIV-1 Entry and Prospects for Protecting against Infection.

Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered.

Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike.

Lipooligosaccharides (LOS) from the bacterium Rhizobium radiobacter Rv3 are structurally related to antigenic mammalian oligomannoses on the HIV-1 envelope glycoprotein spike that are targets for broadly neutralizing antibodies. Here, we prepared a hybrid structure of viral and bacterial epitopes as part of a vaccine design strategy to elicit oligomannose-specific HIV-neutralizing antibodies using glycoconjugates based on the Rv3 LOS structure. Starting from a KdoGlcNAc tetrasaccharide precursor, a central orthogonally protected mannose trichloroacetimidate donor was coupled to OH-5 of the innermost Kdo residue.

Prospective evaluation of the adaptive immune response to SlpA in Clostridium difficile infection.

Clostridium difficile is a major cause of healthcare-associated diarrhea. SlpA is the precursor of the S-layer of C. difficile.

Protection against Clostridium difficile infection in a hamster model by oral vaccination using flagellin FliC-loaded pectin beads.

Clostridium difficile flagellin FliC is a highly immunogenic pathogen-associated molecular pattern playing a key role in C. difficile pathogenesis and gut colonization. Here, we designed an oral vaccine against C.

Targeting Surface Components to Develop Immunotherapeutic Strategies Against Infection.

New therapies are needed to prevent and treat infection and to limit the rise in antibiotic resistance. Besides toxins, several surface components have been characterized as colonization factors and have been shown as immunogenic. This review will focus on passive and active immunization strategies targeting surface components to combat .

Immunization Strategies Against Clostridium difficile.

C. difficile infection (CDI) is an important healthcare- but also community-associated disease. CDI is considered a public health threat and an economic burden.

Clostridium difficile flagellin FliC: Evaluation as adjuvant and use in a mucosal vaccine against Clostridium difficile.

The immunogenicity of bacterial flagellin has been reported in different studies. By its close interaction with the immune system, the flagellin represents an interesting adjuvant and vaccine candidate. Salmonella Typhimurium flagellin has already been tested as adjuvant to stimulate mucosal immunity.

Immunogenic properties of the surface layer precursor of Clostridium difficile and vaccination assays in animal models.

Clostridium difficile is an opportunistic pathogen causing gut inflammation generally associated with an intestinal dysbiosis due to antibiotics. Several virulence factors have been identified as playing a key role in gut colonization. The surface-layer proteins, comprised of two proteins, the high molecular weight SlpA (HMW-SLP) and the low molecular weight SlpA (LMW-SLP), are the most abundant proteins on the C.

Effectiveness of antiviral treatment on acute phase of herpes zoster and development of post herpetic neuralgia: review of international publications.

Herpes zoster is due to the reactivation of the virus causing varicella, called varicella-zoster virus. It affects peripheral nerves and causes painful skin and nerve lesions. This pain may last for months, or years after the initial lesions have resolved: post-herpetic neuralgia is the most frequent complication.

Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial.

Background And Objective: Post-herpetic neuralgia (PHN) is a distressing neuropathic pain condition mainly affecting elderly patients. Neuropathic pain symptoms can be of a burning, shooting and stabbing nature, and may continue for prolonged periods and are often poorly controlled by polymedication. The aim of this study was to evaluate the analgesic efficacy and safety of topical analgesic treatment (5% lidocaine [lignocaine] medicated plaster) compared with placebo plaster in patients with PHN.

Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).

Few studies have directly compared the clinical features of neuropathic and non-neuropathic pains. For this purpose, the French Neuropathic Pain Group developed a clinician-administered questionnaire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination. This questionnaire was used in a prospective study of 160 patients presenting with pain associated with a definite neurological or somatic lesion.

Characteristics of patients with herpes zoster on presentation to practitioners in France.

There have been many epidemiological studies of chickenpox but only a few of herpes zoster. We report data from an observational study, conducted in France during a 1-year period, of 9038 patients who presented with acute herpes zoster (n = 8103) or postherpetic neuralgia (PHN; n = 935) at the office practices of 4635 general practitioners or dermatologists. The incidence of herpes zoster in France was found to be similar to that in the literature: from 1.

[Prevalence and management of pain in a hospital: a cross-sectional study].

Objectives: Improved management of pain, particularly in inpatients, is a public health priority. We conducted this study to ascertain current practices and identify indications useful for measuring their impact.

Patients And Methods: A "given day" cross-sectional study was conducted in 18 units (11 medicine units and 7 surgery and obstetrics units) at the Cochin Hospital, Paris.

How should zoster trials be conducted?

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes zoster. They agreed that trials in herpes zoster should have prospectively agreed definitions of all outcome measures and plans for data analysis. In immunocompetent individuals, in whom pain is the major outcome measure, trials should only include patients over the age of 50 years, and for those recruited within 72 h of rash onset, should be designed to demonstrate superiority of any new therapy over existing antivirals.

Prospective epidemiologic study of painful and neurologic sequelae induced by herpes zoster in patients treated early with oral acyclovir.

Three hundred and one patients with acute herpes zoster treated early with oral acyclovir were enrolled in an open, prospective study designed to evaluate painful and neurologic disorders over a 6-month period. Age, initial pain severity, and occurrence of a neurologic deficit influenced the incidence of postherpetic neuralgia. No relationship was found between initial rash severity and either pain incidence or neurologic deficit.

[Placebo effect in the treatment of pain].

The placebo induces a significant analgesia on average in 35% patients with some variations according to the studied pathology and the modalities of the therapy. This placebo effect is especially influenced by the expectations and beliefs of the patient, the doctor, the environment and the quality of the doctor-patient relationship. As with a real psychogenic analgesia, this effect could partly result in a release of endogenous opioid substances.

Substance P levels in the synovium and synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA.

[Does the differential block by the epidural route provide a diagnostic aid in chronic pain?].

Sixty-two patients with chronic pain below the waist level were evaluated with a differential epidural block performed after an overall somatic and psychological assessment. The pain and neurophysiologic variations under block were compared with the somatic and psychological findings. No consistent relationship was found between pain variations and sympathetic sensory effects of the graduated epidural block.