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Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: Intra-nasal vaccination
- Source :
- Vaccine. 26:664-676
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Vaccinia virus (VACV) has been used as the vaccine to protect against smallpox, and recombinant VACVs have been used to develop vaccine candidates against numerous cancers and infectious diseases. Although relatively safe for use in humans, the strains of VACV that were used as smallpox vaccines led to several complications including, progressive infection in immune compromised individuals, eczema vaccination in individuals with a history of atopic dermatitis, and encephalitis and perimyocarditis in apparently healthy individuals. The work described in this paper focuses on attenuated strains of VACV that may have the potential for use as vaccine vectors with reduced pathogenicity. We have generated several VACV mutants in a WR background with specific mutations in the E3L gene that were at least a 1000-fold less pathogenic compared to wtVACV upon intra-nasal infection of mice. Many of these mutant viruses replicated to high titers in the nasal mucosa of mice following intra-nasal administration. Despite replication to high titers in the nose, there was little spread to other organs in infected animals. Intra-nasal vaccination with doses as low as 100-1000 pfu (plaque forming units) of these replicating VACV constructs were sufficient to protect the host from challenge with large doses of wtVACV. Similar constructs in a Copenhagen and a NYCBH background were highly attenuated, yet effective as vaccines in the mouse model. These recombinant VACV constructs may be promising vector candidates for use in vaccination strategies against smallpox and other pathogens.
- Subjects :
- Male
viruses
Drug Evaluation, Preclinical
Vaccinia virus
Mice, SCID
Vaccines, Attenuated
Article
Cell Line
Mice
Viral Proteins
Animals
Humans
Administration, Intranasal
Virulence
General Veterinary
General Immunology and Microbiology
Vaccination
Public Health, Environmental and Occupational Health
virus diseases
RNA-Binding Proteins
Mice, Inbred C57BL
Infectious Diseases
Mutation
Molecular Medicine
Female
Smallpox Vaccine
Smallpox
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....7985d8422cb9c2f7edd56df1f65ad4f0