Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines

Intra-nasal vaccination

Sangeetha Vijaysri, Garilyn Jentarra, Michael C. Heck, Andrew A. Mercer, Colin J. McInnes, Bertram Jacobs

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 vaccinatum 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.

Original languageEnglish (US)
Pages (from-to)664-676
Number of pages13
JournalVaccine
Volume26
Issue number5
DOIs
StatePublished - Jan 30 2008

Fingerprint

Attenuated Vaccines
Vaccinia virus
live vaccines
Nose
Vaccination
vaccination
mutation
Mutation
Vaccines
vaccines
Genes
Smallpox
genes
Kaposi Varicelliform Eruption
Smallpox Vaccine
eczema
intranasal administration
nasal mucosa
vector vaccines
Intranasal Administration

Keywords

  • E3L
  • Interferon-resistance
  • Smallpox vaccine
  • Vaccinia virus

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines : Intra-nasal vaccination. / Vijaysri, Sangeetha; Jentarra, Garilyn; Heck, Michael C.; Mercer, Andrew A.; McInnes, Colin J.; Jacobs, Bertram.

In: Vaccine, Vol. 26, No. 5, 30.01.2008, p. 664-676.

Research output: Contribution to journalArticle

Vijaysri, Sangeetha ; Jentarra, Garilyn ; Heck, Michael C. ; Mercer, Andrew A. ; McInnes, Colin J. ; Jacobs, Bertram. / Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines : Intra-nasal vaccination. In: Vaccine. 2008 ; Vol. 26, No. 5. pp. 664-676.
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