title: One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.
abstract: To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate.
authors.affiliation: AIDS Center and Modern Virology Research Center, State Key Laboratory of Virology, College of Life Sciences, Wuhan University, PR China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Fang
authors.forename: Weijun
authors.initials: W
authors.lastname: Zhu
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009500:Neutralization Tests; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014709:Vero Cells; D014774:Virulence
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated