Covalent decoration of adenovirus vector capsids with the carbohydrate epitope αGal does not improve vector immunogenicity, but allows to study the in vivo fate of adenovirus immunocomplexes.

Adenovirus-based vectors are promising tools for genetic vaccination. However, several obstacles have to be overcome prior to a routine clinical application of adenovirus-based vectors as efficacious vectored vaccines. The linear trisaccharide epitope αGal (alpha-Gal) with the carbohydrate sequence galactose-α-1,3-galactosyl-ß-1,4-N-acetylglucosamine has been described as a potent adjuvant for recombinant or attenuated vaccines. Humans and α-1,3-galactosyltransferase knockout mice do not express this epitope. Upon exposure of α-1,3-galactosyltransferase-deficient organisms to αGal in the environment, large amounts of circulating anti-Gal antibodies are produced consistently. Immunocomplexes formed between recombinant αGal-decorated vaccines and anti-Gal antibodies exhibit superior immunogenicity. We studied the effects of the trisaccharide epitope on CD8 T cell responses that are directed specifically to vector-encoded transgenic antigens. For that, covalently αGal-decorated adenovirus vectors were delivered to anti-Gal α-1,3-galactosyltransferase knockout mice. We generated replication-defective, E1-deleted adenovirus type 5 vectors that were decorated with αGal at the hexon hypervariable regions 1 or 5, at fiber knob, or at penton base. Surprisingly, none of the adenovirus immunocomplexes being formed from αGal-decorated adenovirus vectors and anti-Gal immunoglobulins improved the frequencies of CD8 T cell responses against the transgenic antigen ovalbumin. Humoral immunity directed to the adenovirus vector was neither increased. However, our data indicated that decoration of Ad vectors with the αGal epitope is a powerful tool to analyze the fate of adenovirus immunocomplexes in vivo.

Ocorrência de hospitalizações de idosos por quedas / Occurrence of falls in elderly hospitalizations

Pesquisa exploratória/descritiva cujos objetivos foram identificar o perfil sociodemográfico de idosos hospitalizados em decorrência de quedas; investigar a ocorrência/fatores relacionados à hospitalização dos idosos por quedas. Utilizou-se um instrumento estruturado e a análise foi realizada pelos valores numéricos por meio do programa Microsoft Excel for Windows. A pesquisa recebeu parecer favorável pelo Comitê de Ética em Pesquisa da Universidade de Cruz Alta, sob número CAAE - 0002.0.417.000-09. Evidenciou-se que a queda atinge ambos os sexos, com predominância do sexo feminino, e a idade acima dos 80 anos. Do total de quatorze idosos, identificou-se que dez sofreram quedas da própria altura e ocorreram durante a realização das atividades de vida diárias. Dentre todos os eventos envolvendo quedas ocorreu um óbito. Do total de idosos, sete apresentaram fratura de fêmur e o tratamento realizado para a maioria dos casos foi cirúrgico. Espera-se através desta pesquisa, contribuir para minimizar a vulnerabilidade dos idosos no que se refere às quedas, auxiliando na prevenção/cuidado por meio da elaboração de ações/estratégias viáveis, com intuito de melhorar a qualidade de vida dessa população.

This exploratory/descriptive whose objectives were to identify the socio-demographic profile of elderly hospitalized due to falls; investigate the occurrence or factors related to hospitalization of the elderly from falls. It was used a structured instrument and the analysis was performed by numerical values through the Microsoft Excel for Windows program. The research approved by the Ethics Committee in Research of the University of Cruz Alta, under number CAAE - 0002.0.417.000-09. It became evident that the fall affects both genders, with female predominance, and age above 80 years old. From the fourteen elderly identified, ten suffered falls from height and these occurred during the performance of activities of daily living. Among all events involving elderly falls, occurred one casualty. In this elderly group, seven had a femur fracture and treatment performed for most cases had to be surgical. It is expected through this research contribute to minimize the vulnerability of the elderly with regard to falls , helping in the prevention and care through the development of suitable actions or strategies, in order to improve the quality of life of this population

Traceless bioresponsive shielding of adenovirus hexon with HPMA copolymers maintains transduction capacity in vitro and in vivo.

Capsid surface shielding of adenovirus vectors with synthetic polymers is an emerging technology to reduce unwanted interactions of the vector particles with cellular and non-cellular host components. While it has been shown that attachment of shielding polymers allows prevention of undesired interactions, it has become evident that a shield which is covalently attached to the vector surface can negatively affect gene transfer efficiency. Reasons are not only a limited receptor-binding ability of the shielded vectors but also a disturbance of intracellular trafficking processes, the latter depending on the interaction of the vector surface with the cellular transport machinery. A solution might be the development of bioresponsive shields that are stably maintained outside the host cell but released upon cell entry to allow for efficient gene delivery to the nucleus. Here we provide a systematic comparison of irreversible versus bioresponsive shields based on synthetic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. In addition, the chemical strategy used for generation of the shield allowed for a traceless bioresponsive shielding, i.e., polymers could be released from the vector particles without leaving residual linker residues. Our data demonstrated that only a bioresponsive shield maintained the high gene transfer efficiency of adenovirus vectors both in vitro and in vivo. As an example for bioresponsive HPMA copolymer release, we analyzed the in vivo gene transfer in the liver. We demonstrated that both the copolymer's charge and the mode of shielding (irreversible versus traceless bioresponsive) profoundly affected liver gene transfer and that traceless bioresponsive shielding with positively charged HPMA copolymers mediated FX independent transduction of hepatocytes. In addition, we demonstrated that shielding with HPMA copolymers can mediate a prolonged blood circulation of vector particles in mice. Our results have significant implications for the future design of polymer-shielded Ad and provide a deeper insight into the interaction of shielded adenovirus vector particles with the host after systemic delivery.