Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria Vaccine Adjuvanted with Alhydrogel™, Montanide ISA 720 or AS02

Contains fulltext : 71100.pdf (publisher's version ) (Open Access)BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 microg and 50 microg doses with three different adjuvants, Alhydrogel, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8-10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80-100%). Induration occurred in the Montanide 50 microg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1-2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNgamma and IL-5 cytokines. CONCLUSIONS/SIGNIFICANCE: All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies. TRIAL REGISTRATION: (Clinicaltrials.gov) NCT00730782

Dental pulp tissue engineering

Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research

A successful case of biological invasion: the fish Cichla piquiti, an Amazonian species introduced into the Pantanal, Brazil

The "tucunaré", Cichla piquiti, an exotic Amazonian fish has become established along the left bank of the Paraguay River in the Pantanal. It was introduced by escaping from culture ponds in the Upper Piquiri River and spread downstream, along the lateral flooded areas of that river, continuing through the clear waters of the left bank of the Paraguay River and reaching south as far as the Paraguai Mirim and Negrinho rivers. Adult spawners have been found in the region, meaning that it is a self-sustained population. Reproduction occurs in the period of low waters. They were found feeding on fishes of lentic environments belonging to the families Characidae, Cichlidae and Loricariidae. Until the end of 2004, its distribution was restricted to the left bank of the Paraguay River, but in March 2005, some specimens were found on the right bank, raising a question for the future: what will be the distribution area of the tucunaré in the Pantanal? Information about its dispersion is increasing: it is known to be in the Tuiuiú Lake, Pantanal National Park and in the Bolivian Pantanal, all of them on the right bank of the Paraguay River. The hypothesis that the "tucunaré" could not cross turbid waters, such as in the Paraguay River, was refuted by these recent findings. Possibly, the tucunaré's capacity to lay more than one batch of eggs in a reproductive period, as well as its care of eggs and young, lead them to establish themselves successfully in new environments, as has been observed in the Pantanal and other localities