Novel chimeric E2CD154 subunit vaccine is safe and confers long lasting protection against classical swine fever virus.

E2CD154 is a vaccine candidate against classical swine fever (CSF) based on a chimeric protein composed of the E2 glycoprotein fused to porcine CD154 antigen, and formulated in the oil adjuvant Montanide™ ISA 50 V2. This vaccine confers early protection in pigs and prevents vertical transmission in pregnant sows. The objectives of this study were to assess the safety of this immunogen in piglets, to compare several doses of antigen in the formulation, and to study the duration of the immunity provided by this vaccine for up to 9 months. Three trials were conducted by immunizing pigs with a two-dose regime of the vaccine. Challenge experiments were carried out with the highly pathogenic Margarita strain. No local or systemic adverse effects were documented, and neither macroscopic nor microscopic pathological findings were observed in the vaccinated animals. The three antigen doses explored were safe and induced CSF protective neutralizing antibodies. The dose of 50 µg was selected for further development because it provided the best clinical and virological protection. Finally, this protective immunity was sustained for at least 9 months. This study demonstrates that E2CD154 vaccine is safe; defines a vaccine dose of 50 µg antigen, and evidences the capacity of this vaccine to confer long term protection from CSFV infection for up to 9 months post- vaccination. These findings complement previous data on the evaluation of this vaccine candidate, and suggest that E2CD154 is a promising alternative to modified live vaccines in CSF endemic areas.

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism.

In nonstimulated rabbit gastric glands, acetylsalicylic acid (10-500 microM) and indomethacin (3-300 microM) did not significantly modify the basal rate of acid secretion, whereas diclofenac and piroxicam (10-1,000 microM each) caused a marked and dose-dependent inhibitory effect (EC(50) = 138 and 280 microM, respectively). In gastric glands stimulated by histamine (100 microM), diclofenac also reduced the rate of acid formation in a dose-dependent manner. In contrast, acetylsalicylic acid, indomethacin, and piroxicam exerted a biphasic effect; thus low concentrations (3-100 microM) of these three agents significantly increased the rate of histamine-stimulated acid secretion (10-20% over the corresponding control value) by a cAMP-independent mechanism, whereas higher concentrations reduced the rate of acid formation. With respect to underlying biochemical mechanisms that could mediate inhibitory effects of NSAIDs on gastric acid formation, it was observed that both diclofenac and piroxicam, but not acetylsalicylic acid or indomethacin, decreased the glandular content of ATP, inhibited hydrolytic activity of gastric gland microsomal H(+)-K(+)-ATPase, and reduced the rate of H(+)-K(+)-ATPase-dependent proton transport across microsomal membranes in a dose-dependent manner. Furthermore, diclofenac and piroxicam also significantly increased passive permeability of microsomal membranes to protons. In conclusion, our work shows that diclofenac and piroxicam cause a significant reduction in the rate of basal and histamine-stimulated acid formation in isolated rabbit gastric glands at concentrations that can be attained in the gastric lumen of patients treated with these drugs. Mechanisms involved in these inhibitory effects appear to be multifocal and include different steps of stimulus-secretion coupling.