title: Newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats.
abstract: Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10⁹·⁸ 50% egg infective doses (EID₅₀)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10⁸·³ EID₅₀ completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.
authors.affiliation: Harbin Veterinary Research Institute, CAAS, 427 Maduan Street, Harbin 150001, People's Republic of China. zgbu@yahoo.com.
authors.forename: Jinying
authors.initials: J
authors.lastname: Ge
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
authors.forename: Lihong
authors.initials: L
authors.lastname: Tao
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wen
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
authors.forename: Chinglai
authors.initials: C
authors.lastname: Yang
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D002415:Cats; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004285:Dogs; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D009522:Newcastle disease virus / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D011819:Rabies Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins