SIV escape mutants in rhesus macaques vaccinated with NEF-derived lipopeptides and challenged with pathogenic SIVmac251

BACKGROUND: Emergence of viral variants that escape CTL control is a major hurdle in HIV vaccination unless such variants affect gene regions that are essential for virus replication. Vaccine-induced multispecific CTL could also be able to control viral variants replication. To explore these possibilities, we extensively characterized CTL responses following vaccination with an epitope-based lipopeptide vaccine and challenge with pathogenic SIVmac251. The viral sequences corresponding to the epitopes present in the vaccine as well as the viral loads were then determined in every macaque following SIV inoculation. RESULTS: In most cases, the emergence of several viral variants or mutants within vaccine CTL epitopes after SIV challenge resulted in increased viral loads except for a single macaque, which showed a single escape viral variant within its 6 vaccine-induced CTL epitopes. CONCLUSION: These findings provide a better understanding of the evolution of CD8+ epitope variations after vaccination-induced CTL expansion and might provide new insight for the development of an effective HIV vaccine

Antihistamine‐resistant chronic spontaneous urticaria remains undertreated: 2‐year data from the AWARE study

Background: Real-world evidence describing the benefits of recommended therapies and their impact on the quality of life (QoL) of chronic urticaria (CU) patients is limited. Objective: To investigate disease burden, current treatment schedule, and the use of clinical resources by patients with H1 -antihistamine-refractory CU in Europe. Methods: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global, prospective, non-interventional study in the real-world setting, sponsored by the manufacturer of omalizumab. Disease characteristics, pharmacological treatments, and health-related QoL of patients (N = 2727) ≥18 years of age diagnosed with H1 -antihistamine-refractory chronic spontaneous urticaria (without inducible urticaria) for >2 months are reported here. Results: Of the 2727 patients included, 1232 (45.2%) and 1278 (46.9%) were successfully followed up for any assessment and for the key outcome, the urticaria control test (UCT) score, respectively, and patients with complete remission (14.1%) were excluded from analyses.The proportion of patients with uncontrolled CSU (UCT score <12) dropped from 78% (n/N = 1641/2104) at baseline to 28.7% (n/N = 269/936) after two years of participation in the AWARE study. In addition, the proportion of patients with no impact of CSU on their QoL (assessed by the Dermatological Life Quality Index) increased to 57% (n/N = 664/1164) from 18.7% (n/N = 491/2621) at baseline. Emergency room visits (2.4% [n/N = 7/296] vs 33.5% [n/N = 779/2322]) and hospital stays (1.7% [n/N = 5/296] vs 24.2% [n/N = 561/2322]) reduced at Month 24 vs baseline. Overall, 23.2% (n/N = 26/112) patients on non-sedating H1 -antihistamines (nsAH) and 41.9% (n/N = 44/105) patients on up-dosed nsAH had uncontrolled CSU (UCT <12) at Month 24. In omalizumab-treated patients, 27.1% (n/N = 78/288) had uncontrolled CSU at Month 24. Conclusion: These data confirm improvements for most patients with CSU over a 2-year follow-up period. Further studies are needed to understand the differences between guideline recommendations and reported management

Maladie de Rendu Osler révélée par des télangiectasies oro-faciales

Introduction : La maladie de Rendu Osler (MRO) est une maladie génétique autosomique dominante liée à un trouble de l’angiogenèse. Son incidence est en moyenne de 1 pour 5000 habitants. Son diagnostic est basé sur la présence de télangiectasies cutanéo-muqueuses, des épistaxis récidivantes, des malformations artério-veineuses viscérales et un contexte héréditaire. Observation : Le cas d’une patiente atteinte de MRO a été diagnostiqué au cours d’une consultation odontologique de routine. Le bilan a mis en évidence des malformations vasculaires viscérales. Un diagnostic familial a également été réalisé. Discussion : La MRO possède de nombreuses formes cliniques. Un dépistage précoce est indispensable pour détecter les malformations artério-veineuses (MAV). Les MAV peuvent avoir de multiples complications en fonction de leur taille et de leur siège. Le traitement de la MRO se focalise sur les MAV. Les molécules modulatrices de l’angiogenèse constituent une thérapeutique d’avenir

Type 1 CD4(+) T-Cell Help Is Required for Induction of Antipeptide Multispecific Cytotoxic T Lymphocytes by a Lipopeptidic Vaccine in Rhesus Macaques

We have optimized the induction of antiviral cytotoxic T lymphocytes (CTL) in rhesus macaques by a lipopeptide vaccine containing seven peptides from simian immunodeficiency virus (SIV) Nef and Gag proteins and a strong T-helper peptide from tetanus toxoid (TT) that is promiscuous in humans (peptide TT 830-846). Two of the eight immunized macaques showed T-helper (Th) cell proliferation and a specific synthesis of gamma interferon in response to TT 830-846 peptide. They also showed multispecific cytotoxic activity against three to five of the immunizing SIV peptides. These results show the importance of a strong specific type 1 Th response for inducing a multispecific CTL response in vivo, which is essential for the development of an anti-human immunodeficiency virus vaccine

Antihistamine‐resistant chronic spontaneous urticaria remains undertreated : 2‐year data from the AWARE study

Background Real-world evidence describing the benefits of recommended therapies and their impact on the quality of life (QoL) of chronic urticaria (CU) patients is limited. Objective To investigate disease burden, current treatment schedule, and the use of clinical resources by patients with H-1-antihistamine-refractory CU in Europe. Methods AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global, prospective, non-interventional study in the real-world setting, sponsored by the manufacturer of omalizumab. Disease characteristics, pharmacological treatments, and health-related QoL of patients (N = 2727) >= 18 years of age diagnosed with H-1-antihistamine-refractory chronic spontaneous urticaria (without inducible urticaria) for >2 months are reported here. Results Of the 2727 patients included, 1232 (45.2%) and 1278 (46.9%) were successfully followed up for any assessment and for the key outcome, the urticaria control test (UCT) score, respectively, and patients with complete remission (14.1%) were excluded from analyses.The proportion of patients with uncontrolled CSU (UCT score <12) dropped from 78% (n/N = 1641/2104) at baseline to 28.7% (n/N = 269/936) after two years of participation in the AWARE study. In addition, the proportion of patients with no impact of CSU on their QoL (assessed by the Dermatological Life Quality Index) increased to 57% (n/N = 664/1164) from 18.7% (n/N = 491/2621) at baseline. Emergency room visits (2.4% [n/N = 7/296] vs 33.5% [n/N = 779/2322]) and hospital stays (1.7% [n/N = 5/296] vs 24.2% [n/N = 561/2322]) reduced at Month 24 vs baseline. Overall, 23.2% (n/N = 26/112) patients on non-sedating H-1-antihistamines (nsAH) and 41.9% (n/N = 44/105) patients on up-dosed nsAH had uncontrolled CSU (UCT <12) at Month 24. In omalizumab-treated patients, 27.1% (n/N = 78/288) had uncontrolled CSU at Month 24. Conclusion These data confirm improvements for most patients with CSU over a 2-year follow-up period. Further studies are needed to understand the differences between guideline recommendations and reported management

The Use of Monoclonal Antibody to Keratin in Human Epidermal Disease: Alterations in Immunohistochemical Staining Pattern

A monoclonal antikeratin antibody, designated AE1, was used to stain frozen sections of normal and abnormal human skin by the immunofluorescence and peroxidase-antiperoxidase techniques. In normal human epidermis and ichthyosis vulgaris, a nonproliferative epidermal disease, this antibody selectively stained epidermal basal cells. Very different staining patterns were observed in various other epidermal diseases. A suprabasal staining pattern was observed in psoriasis (16 cases), verruca (9), seborrheic keratosis (5), actinic keratosis (2), as well as the epidermis adjacent to certain epidermal neoplasms (4). Basal cell carcinoma (7) showed weak, homogeneous staining. In contrast, a disorganized pattern consisting of cells with various staining intensities was observed in Bowen's disease (2) and squamous cell carcinoma (4). Although the biochemical basis for these altered staining patterns remains to be elucidated, these results provide further evidence that epidermal keratin expression can be affected by various disease states. Moreover, our data suggest that a common alteration in keratin expression, as defined by the suprabasal AE1 staining pattern, exists in psoriasis and a number of other benign hyperproliferative epidermal diseases