Induction of Neutralizing Antibody Responses to Anthrax Protective Antigen by Using Influenza Virus Vectors: Implications for Disparate Immune System Priming Pathways▿

• Type of Material: Article
• Authors: William A. Langley, Emory University; Konrad C. Bradley, Emory University; Zhu-Nan Li, Emory University; Mary Ellen Smith, Emory University; Matthias J. Schnell, Emory University; David Steinhauer, Emory University
• Language: English
• Date: 2010-08
• Publisher: American Society for Microbiology (ASM)
• Publication Version: Final Published Version
• Copyright Statement: © 2010, American Society for Microbiology
• Final Published Version (URL): http://jvi.asm.org/content/84/16/8300
• Title of Journal or Parent Work: Journal of Virology
• Volume: 84
• Issue: 16
• Start Page: 8300
• End Page: 8307
• Grant/Funding Information: This study was supported by NIH Public Health Service grant from NIAID AI/EB53359 and contract HHSN266200700006C to D.A.S. and grant R41AI063822 to M.J.S. and by the Emory Center for AIDS Research (P30AI050409).
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Viral vectors based on influenza virus, rabies virus (RV), and vaccinia virus (VV) were used to express large polypeptide segments derived from the Bacillus anthracis protective antigen (PA). For the infectious influenza virus vector and recombinant VV constructs, the receptor binding domain (RBD or domain 4) or the lethal and edema factor binding domain (LEF or domain 1′) were engineered into functional chimeric hemagglutinin (HA) glycoproteins. In the case of the RV vector, the viral glycoprotein (G) was used as a carrier for RBD in an inactivated form of the vector. These constructs were examined by using multiple homologous and heterologous prime/boost immunization regimens in order to optimize the induction of α-PA antibody responses. Several immunization combinations were shown to induce high titers of antibody recognizing the anthrax RBD and LEF domains, as well as the full-length PA protein in mice. The heterologous prime/boost immunization regimens that involved an initial intranasal administration of a live influenza virus vector, followed by an intramuscular boost with either the killed RV vector or the VV vector, were particularly effective, inducing antigen-specific antibodies at levels severalfold higher than homologous or alternative heterologous protocols. Furthermore, sera from several groups of the immunized mice demonstrated neutralization activity in an in vitro anthrax toxin neutralization assay. In some cases, such toxin-neutralizing activity was notably high, indicating that the mechanisms by which immunity is primed by live influenza virus vectors may have beneficial properties.