Antibodies induced by dengue virus type 1 and 2 envelope domain III recombinant proteins in monkeys neutralize strains with different genotypes.

In this study, we evaluated the capacity of neutralizing antibodies induced by dengue virus types 1 and 2 envelope domain III of recombinant proteins in monkeys against a different strain of dengue virus types 1 and 2 genotype. Here Swine Recombinant Proteins we show that the dengue virus types 1 and 2 recombinant protein induced high titers of antibodies to strains of different genotypes.

Organ uptake in the brain and in Vivo Rhesus monkeys of recombinant Iduronidase Compared with Insulin Receptor Antibody-Iduronidase Fusion Protein.

Mucopolysaccharidosis type I (MPsi) is caused by mutations in the gene encoding the lysosomal enzyme, α-L-iduronidase (IDUA), and patients with MPsi currently being treated with IDUA enzyme replacement therapy (ERT). However, the majority of patients MPsi have severe CNS involvement, and conventional ERT did not treat brain. ERT failure to treat the brain believed to be due to the lack of transport IDUA through the blood-brain barrier (BBB). However, the BBB transport IDUA not been measured directly, until now. 

BBB IDUA transport can be enhanced by fusion enzymes to monoclonal antibodies (mAb) against human insulin receptor (HIR). The HIRMAb binding to insulin receptors on the BBB transport into the brain triggers and act as a molecular Trojan horse to give IDUA to brain cells. Therefore, the aim of this study was to compare, side-by-side, the BBB transport of IDUA alone and fusion protein-IDUA HIRMAb in Rhesus monkeys in vivo. 

Each protein is radio-iodinated by conjugation Bovine Recombinant Proteins with [125I] -Bolton-Hunter reagent and was injected intravenously (IV) in primates. Absorption by the brain and peripheral organs, measured by whole body autoradiography. The results showed no transport of IDUA only into the brain, but that brain uptake of fusion protein IDUA HIRMAb-high, 1.2% injected dose / brain. 

There is a comparable absorption of IDUA and HIRMAb-IDUA fusion protein by peripheral organs, in which the absorption is mainly controlled by the mannose 6-phosphate receptor. The work demonstrates that treatment with fusion protein HIRMAb MPsi-IDUA be as effective as IDUA in peripheral organs, but offers the benefits of the treatment of the central nervous system in MPsi.