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Protection of Mice by Equine Herpesvirus Type 1–Based Experimental Vaccine against Lethal Venezuelan Equine Encephalitis Virus Infection in the Absence of Neutralizing Antibodies

A vectored vaccine based on equine herpesvirus type 1 (EHV-1) was generated as an alternative for safe and efficient prophylaxis against Venezuelan equine encephalitis virus (VEEV) infection. Two-step (en passant) Red mutagenesis was used to insert VEEV structural genes into an infectious clone of EHV-1 vaccine strain RacH. The recombinant virus, rH_VEEV, efficiently and stably expressed VEEV structural proteins as detected by various antibodies, including a conformation-dependent monoclonal antibody to envelope glycoprotein E2. In addition, rH_VEEV was indistinguishable from parental bacterial artificial chromosome–derived virus with respect to growth properties in cultured cells. Immunization of mice with the vectored vaccine conferred full protection against lethal challenge infection using VEEV strain ZPC738 in the absence of neutralizing antibodies and in a dose-dependent manner. Analyses of IgG responses demonstrated production of VEEV-specific IgG1 and total IgG antibodies after vaccination, indicating that protection was dependent on either cytotoxic T cell responses or antibody-mediated protection unrelated to neutralizing activity.

Received September 24, 2006. Accepted for publication June 13, 2007.

Acknowledgments: We would like to thank Jennifer Smith for technical assistance and Kerstin Osterrieder for statistical analysis.

Financial support: This study work was supported by National Institutes of Health (NIH) grant AI061412 and the Harry M. Zweig Memorial Fund for Equine Research (to Nikolaus Osterrieder). Slaoboaan Paessler was supported by NIH K08 grant AI059491.

^* Address correspondence to Nikolaus Osterrieder, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail: no34{at}cornell.edu

Authors’ addresses: Cristina Rosas, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, Telephone: 607-253-4014, Fax: 607-253-3384, E-mail: ctr8{at}cornell.edu. Slobodan Paessler, Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, Telephone: 409-747-0764, Fax: 409-747-0762, E-mail: slpaessl{at}utmb.edu. Haolin Ni, Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, Telephone: 409-747-2489, Fax: 409-747-0762, E-mail: shni{at}utmb.edu. Nikolaus Osterrieder, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, E-mail: no34{at}cornell.edu.