Protection of mice by equine herpesvirus type 1-based experimental vaccine against lethal Venezuelan equine encephalitis virus infection in the absence of neutralizing antibodies

Cristina T. Rosas, Slobodan Paessler, Haolin Ni, Nikolaus Osterrieder

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume78
Issue number1
StatePublished - Jan 2008
Externally publishedYes

Fingerprint

Venezuelan Equine Encephalitis Viruses
Equid Herpesvirus 1
Virus Diseases
Neutralizing Antibodies
Vaccines
Immunoglobulin G
Herpesvirus Vaccines
Viruses
Viral Structural Proteins
Bacterial Artificial Chromosomes
Antibodies
Infectious Encephalitis
Mutagenesis
Antibody Formation
Cultured Cells
Immunization
Glycoproteins
Vaccination
Clone Cells
Monoclonal Antibodies

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

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abstract = "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.",
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