<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sanne Terryn</style></author><author><style face="normal" font="default" size="100%">Aurélie Francart</style></author><author><style face="normal" font="default" size="100%">Lamoral, Sophie</style></author><author><style face="normal" font="default" size="100%">Hultberg, Anna</style></author><author><style face="normal" font="default" size="100%">Rommelaere, Heidi</style></author><author><style face="normal" font="default" size="100%">Wittelsberger, Angela</style></author><author><style face="normal" font="default" size="100%">Callewaert, Filip</style></author><author><style face="normal" font="default" size="100%">Stohr, Thomas</style></author><author><style face="normal" font="default" size="100%">Meerschaert, Kris</style></author><author><style face="normal" font="default" size="100%">Ottevaere, Ingrid</style></author><author><style face="normal" font="default" size="100%">Stortelers, Catelijne</style></author><author><style face="normal" font="default" size="100%">Vanlandschoot, Peter</style></author><author><style face="normal" font="default" size="100%">Kalai, Michael</style></author><author><style face="normal" font="default" size="100%">Steven Van Gucht</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Protective effect of different anti-rabies virus VHH constructs against rabies disease in mice.</style></title><secondary-title><style face="normal" font="default" size="100%">PLoS One</style></secondary-title><alt-title><style face="normal" font="default" size="100%">PLoS One</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Neutralizing</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Viral</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Disease Models, Animal</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Half-Life</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin Heavy Chains</style></keyword><keyword><style  face="normal" font="default" size="100%">mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Rabies</style></keyword><keyword><style  face="normal" font="default" size="100%">Rabies Vaccines</style></keyword><keyword><style  face="normal" font="default" size="100%">Rabies virus</style></keyword><keyword><style  face="normal" font="default" size="100%">Single-Domain Antibodies</style></keyword><keyword><style  face="normal" font="default" size="100%">Tissue Distribution</style></keyword><keyword><style  face="normal" font="default" size="100%">Viral Load</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">e109367</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable candidates for development of alternative post exposure treatment drugs against rabies.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">10</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/25347556?dopt=Abstract</style></custom1></record></records></xml>