Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Dynamics of transmission of Trypanosoma cruzi in a rural area of Argentina: III. Persistence of T. cruzi parasitemia among canine reservoirs in a two-year follow-up

A new cross-sectional survey of household- associated mongrel dogs as well as follow-up of previously parasitemic individuals was carried out in 1984 toy means of xenodiagnosis and serologic techniques to get a deeper insight into the relationship of T. cruzi parasitemia and age among canine hosts in a rural area of Argentina. Persistence of detectable parasitemia was age-independent, or at most, loosely related to age, confirming the pattern observed in 1982. Similarly no significant age-decreasing effect was recorded among seropositive dogs in: a) the probability of detecting parasites in a 2-year follow-up; b) their intensity of infectiousness (=infective force) for T. infestans 3rd-4th instar nymphs, as measured by the percentage of infected bugs observed in each dog xenodiagnosis. Moreover, not only was the infective force of seropositive dogs for bugs approximately constant through lifetime, but it was significantly higher than the one recorded for children in the present survey, and for human people by other researchers. Therefore, and since T. infestans field populations show high feeding frequencies on dogs, the latter are expected to make the greatest contribution to the pool of infected vectors in the rural household of Argentina. This characteristic should be sufficient to involve canine reservoirs definitely as a risk factor for human people residing in the same house. The increased severity of parasitemia observed among dogs in this survey may be related to the acute undernutrition characteristic of canine populations of poor rural areas in our country, which is expected to affect the ability of the host to manage the infection

Paleobiología de Titanosaurios de Sudamérica: reproducción, desarrollo, histología, neumaticidad, locomoción y neuroanatomía

Much of the current paleobiological knowledge on titanosaur sauropods was attained in just the last fifteen years, in particular that related to reproductive and developmental biology. Recent years have also seen progress on other poorly explored topics, such as pneumaticity, muscle architecture and locomotion, and endocast reconstruction and associated structures. Some titanosaurs laid numerous, relatively small Megaloolithidae eggs (with diameters ranging from 12 to 14 cm) in nests dug In the ground and, as known from the South American records, probably eggs of the multispherulitic morphotype. During ontogeny, certain titanosaurs displayed some variations in cranial morphology, some of them likely associated with the differing feeding habits between hatchlings and adults. The bone tissue of some adult titanosaurs was rapidly and cyclically deposited and shows a greater degree of remodeling than in other sauropods. Saltasaurines in particular show evidence of postcranial skeletal pneumaticity in both axial and appendicular skeleton, providing clues about soft tissue anatomy and the structure of the respiratory system. Titanosaurs, like all sauropods, were characterized by being fully quadrupedal, although some appendicular features and putative trackways indicate that their stance was not as columnar as in other sauropods. These anatomical peculiarities are significantly developed In saltasaurines, a derived group of titanosaurs. Compared with other sauropods, some titanosaurs seem to have had very poor olfaction but would have been capable of capturing sounds In a relatively wide range of high frequencies, although not to the extent of living birds.El conocimiento paleobiológico de los saurópodos titanosaurios, particularmente su reproducción y biología del desarrollo, fue alcanzado recién en los últimos quince años. En estos últimos años también se ha avanzado en temas poco explorados hasta el momento, como la neumatización, su arquitectura muscular y locomoción y la reconstrucción de partes blandas como el cerebro y estructuras asociadas. Algunos titanosaurios depositan sus numerosos y pequeños huevos megaloolitidos en nidos excavados sobre el suelo. Durante la ontogenia ciertos titanosaurios exponen algunas variaciones en su morfología craneana, algunas de estas probablemente asociadas con las diferentes maneras de alimentarse que tendrían los juveniles y los adultos. El tejido óseo de algunos titanosaurios adultos se habría depositado rápido y cíclicamente, exponiendo una mayor remodelación que en otros saurópodos. Los titanosaurios, particularmente los saltasaurinos, exponen una neumaticidad postcraneal en el esqueleto axial y apendicular, este carácter permite Inferir la anatomía de sus tejidos blandos y de su sistema respiratorio. Los titanosaurios, como todos los saurópodos, estaban caracterizados por ser cuadrúpedos, aunque algunos caracteres apendiculares y las huellas indican que su postura no habría sido tan columnar como en otros saurópodos. Aquellas peculiaridades anatómicas están notoriamente desarrolladas en los saltasaurinos, un grupo de titanosaurios derivados. Comparado con otros saurópodos, algunos titanosaurios parecen haber tenido un pobre sentido del olfato, sin embargo estos habrían tenido la capacidad de captar sonidos de alta frecuencia en un rango relativamente amplio, aunque no tanto como las aves actuales.Fil: Garcia, Rodolfo Andres. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salgado, Leonardo. Provincia de Río Negro. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; ArgentinaFil: Cerda, Ignacio Alejandro. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paulina Carabajal, Ariana. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Científico de Paleontología de Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Coria, Rodolfo Anibal. Universidad Nacional de Rio Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiologia y Geologia; Argentina. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiorelli, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica de Anillaco; Argentin