Research Article
Immunization with DNA Vaccine Expressing Gn Coupled to C3d Prevents Clinical Symptoms of Infection and Protects Mice against an Aerosol Rift Valley Fever Virus Infection.
Nitin Bhardwaj1,2, Brooke R. Pierce1 and Ted M. Ross1,2*
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
- *Corresponding Author:
- Ted M. Ross, Ph D
University of Pittsburgh
School of Medicine Center for Vaccine Research
9047 Biomedical Science Tower 3, 3501
Fifth Avenue Pittsburgh, PA 15261, USA
Tel: +1 412 648.8666
Fax: +1 412 624 4440
E-mail: tmr15@pitt.edu
Received Date: November 02, 2011; Accepted Date: December 20, 2011; Published Date: December 29, 2011
Citation: Bhardwaj N, Pierce BR, Ross TM (2012) Immunization with DNA Vaccine Expressing Gn Coupled to C3d Prevents Clinical Symptoms of Infection and Protects Mice against an Aerosol Rift Valley Fever Virus Infection. J Bioterr Biodef S3:006. doi:10.4172/2157-2526.S3-006
Copyright: © 2012 Bhardwaj N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Rift Valley fever virus (RVFV) is the causative agent of Rift Valley fever (RVF) and is an emerging infectious disease of zoonotic potential. However, aerosolization of RVFV has been proposed as a potential bioweapon and most vaccines have not been tested against aerosolized RVFV challenge. Previously, two vaccine platforms (DNA plasmids and alphavirus replicons) expressing a soluble form of the RVFV Gn glycoprotein alone or fused to three copies of complement protein, C3d, protected mice against an intraperitoneal (IP) RVFV infection. In this study, both vaccine candidates were used to determine the protective efficacy against an aerosolized RVFV challenge. Each vaccine was administered to mice alone or in a heterologous prime/replicon boost strategy and anti-RVFV immune responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. However, only Gn-C3d- DNA vaccine completely protected mice against virulent aerosolized RVFV challenge. Most mice receiving replicon based vaccines succumbed to RVFV infection. Surprisingly, even though live-attenuated MP12 vaccine protected mice against IP challenge, MP12 did not provide complete protection against aerosolized RVFV infection. Therefore, vaccine candidates that are effective against peripheral challenge should be tested against aerosolized challenge to determine the complete protection profile, since any bioterrorism attack using RVFV would most likely be in the form of an aerosol.
