Natural Cell-Mediated Cytotoxicity in Cutaneous T-Cell Lymphomas

Natural cell-mediated cytotoxicity was studied in 24 patients with cutaneous T-cell lymphomas and in 18 age- and sex-matched controls studied concomitantly. Percent cytotoxicity was determined by 4-h 51Cr release assay using K562 targets at effector to target ratios of 100:1, 50:1, and 25:1. Mean percent cytotoxicity was significantly lower in patients than in controls at an effector to target cell ratio of 100:1. Likewise, decreased cytotoxicity was found at effector to target ratios of 50:1 and 25:1, although this difference was not significant. When natural killer activity was analyzed separately for males and females, cytotoxicity was lower in both, although the decrease was significant only for male patients. Impairment of natural killer activity did not correlate with blood zinc levels, but appeared to correlate with stage of disease

Transiently Transfected Mammalian Cell Cultures: An Adaptable and Effective Platform for Virus-like Particle-Based Vaccines against Foot-and-Mouth Disease Virus

RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses

Efficacy of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine in cattle using a direct contact transmission model

Abstract Background A direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected ‘seeder’ steers to naïve or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24). In two independent vaccine efficacy trials, AdtA24 was administered once intramuscularly in the neck 7 days prior to contact with FMDV A24/Cruzeiro/BRA/55-infected seeder steers. Results In Efficacy Study 1, we evaluated three doses of AdtA24 to estimate the 50%/90% bovine protective dose (BPD50/90) for prevention of clinical FMD. In vaccinated, contact-challenged steers, the BPD50/90 was 3.1 × 1010 / 5.5 × 1010 AdtA24 particles formulated without adjuvant. In Efficacy Study 2, steers vaccinated with 5 × 1010 AdtA24 particles, exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers, did not develop clinical FMD or transmit FMDV to other vaccinated or naïve, non-vaccinated steers. In contrast, naïve, non-vaccinated steers that were subsequently exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers developed clinical FMD and transmitted FMDV by contact to additional naïve, non-vaccinated steers. The AdtA24 vaccine differentiated infected from vaccinated animals (DIVA) because no antibodies to FMDV nonstructural proteins were detected prior to FMDV exposure. Conclusions A single dose of the AdtA24 non-adjuvanted vaccine conferred protection against clinical FMD at 7 days post-vaccination following direct contact transmission from FMDV-infected, naïve, non-vaccinated steers. The AdtA24 vaccine was effective in preventing FMDV transmission from homologous challenged, contact-exposed, AdtA24-vaccinated, protected steers to co-mingled, susceptible steers, suggesting that the vaccine may be beneficial in reducing both the magnitude and duration of a FMDV outbreak in a commercial cattle production setting

Paediatric otogenic lateral sinus thrombosis: therapeutic management, outcome and thrombophilic evaluation.

OBJECTIVE: Otogenic lateral sinus thrombosis (LST) in children represents a serious condition with potential long-lasting morbidity. The role of adjunct anticoagulation therapy and the benefit of an analysis of prothrombotic factors are unclear. The aim of the study was to report therapeutic management and outcome, analyze prothrombotic factors in children with otogenic LST treated with mastoidectomy/antibiotics/anticoagulation and to evaluate the results with a review of the literature. METHODS: Retrospective chart review of 9 children with otogenic LST (2000-2009) and literature search in PubMed. RESULTS: The most frequent sign was fever in 88%, while neurologic findings were seen in 55%. Streptococci was the most common bacteria (55%). Prothrombotic factors were normal in all children. All patients received therapeutic anticoagulation, without experiencing bleeding complications. Eight children made a full recovery, neurologic sequelae persisted in one. The literature review of 115 children identified fever as the most prominent sign, reported the absence of neurologic findings in almost 50% of cases and confirmed the major role of streptococci. Anticoagulation, as adjunct therapy, was given to 38% of patients in the therapeutic range with a trend towards better neurologic outcome. A prothrombotic analysis was reported in 5 studies with positive results in 2. CONCLUSIONS: Surgery and antibiotics represent the mainstay of the therapy. Anticoagulation can be safely added in view of the high potential for morbidity and might reduce neurologic sequelae. Bacteria with thrombotic activity seem to be an important aetiology. In contrast, a prothrombotic disposition seems to play a minor role in the development of otogenic LST