New vaccines require potent adjuvants like AFPL1 and AFCo1.

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens. AFPL1 is a detergent-extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co-administrated antigens; inducing type I IFN-gamma and IL-12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4(+), TCD8(+), cross-presentation and cytotoxic T-lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1-AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co-administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.

Programmed ventricular stimulation: influence of early versus late introduction of a third extrastimulus, a randomized, prospective study.

OBJECTIVE: The aim of this prospective study was to analyze the yield of early vs late introduction of a third extra-stimulus during programmed ventricular stimulation. METHODS: Two randomized protocols of programmed ventricular stimulation were used in 94 consecutive patients with coronary artery disease who were studied because of non-sustained ventricular tachycardia (9.6%), sustained monomorphic ventricular tachycardia (46.8%), ventricular fibrillation (18.1) or syncope (25.5%). During protocol A, a third extrastimulus was introduced during a basic drive cycle length of 500 ms after completion of programmed ventricular stimulation with 1 and 2 extrastimuli during sinus rhythm and paced cycle lengths of 500, 430. 370 and 330 ms. During protocol B, the third extrastimulus was introduced early (after 1 and 2 extrastimuli during sinus rhythm and a paced cycle length of 500 ms). Both protocols began at the right ventricular apex. If sustained ventricular tachyarrhythmia had been induced, the same sequence of programmed ventricular stimulation was repeated at the right ventricular outflow tract. RESULTS: The overall incidence of induced arrhythmias did not differ between the two protocols. However, the use of the third extrastimulus (both protocols) increased the yield of ventricular fibrillation induction significantly (P < 0.04) compared with ventricular tachycardia induction. CONCLUSIONS: The introduction of the third extrastimulus should be considered only at the end of stimulation protocols (especially in those patients without previously documented sustained ventricular tachyarrhythmias) in order to prevent induction of polymorphic ventricular tachycardia or fibrillation.