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 11,944 bp 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. © 2009 Elsevier Ltd. All rights reserved.