title: Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.
abstract: Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.
authors.affiliation: National Reference Centre of Rabies, Viral Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.|Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
authors.forename: Sanne
authors.initials: S
authors.lastname: Terryn
authors.affiliation: National Reference Centre of Rabies, Viral Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Francart
authors.affiliation: Ablynx NV, Ghent, Belgium.
authors.forename: Heidi
authors.initials: H
authors.lastname: Rommelaere
authors.affiliation: Ablynx NV, Ghent, Belgium.
authors.forename: Catelijne
authors.initials: C
authors.lastname: Stortelers
authors.affiliation: National Reference Centre of Rabies, Viral Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.|Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Van Gucht
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000008:administration & dosage; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D006207:Half-Life; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D056990:Post-Exposure Prophylaxis; D011818:Rabies / Q000401:mortality* / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage*; D011820:Rabies virus; D061905:Single-Domain Antibodies / Q000008:administration & dosage*; D014611:Vaccination; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines; D061905:Single-Domain Antibodies