The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus

Vaccine. 2011 Dec 6;29(52):9691-6. doi: 10.1016/j.vaccine.2011.09.108. Epub 2011 Oct 5.

Abstract

The New York City Board of Health (NYCBH) vaccinia virus (VACV) vaccine strain was deleted for the immune evasion gene, E3L, and tested for its pathogenicity and ability to protect mice from heterologous challenge with ectromelia virus (ECTV). NYCBHΔE3L was found to be highly attenuated for pathogenicity in a newborn mouse model and showed a similar attenuated phenotype as the NYVAC strain of vaccinia virus. Scarification with one or two doses of the attenuated NYCBHΔE3L was able to protect mice equally as well as NYCBH from death, weight loss, and viral spread to visceral organs. A single dose of NYCBHΔE3L resulted in low poxvirus-specific antibodies, and a second dose increased levels of poxvirus-specific antibodies to a level similar to that seen in animals vaccinated with a single dose of NYCBH. However, similar neutralizing antibody titers were observed following one or two doses of NYCBHΔE3L or NYCBH. Thus, NYCBHΔE3L shows potential as a candidate for a safer human smallpox vaccine since it protects mice from challenge with a heterologous poxvirus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Body Weight
  • Cricetinae
  • Ectromelia virus / immunology*
  • Ectromelia, Infectious / immunology
  • Ectromelia, Infectious / mortality
  • Ectromelia, Infectious / pathology
  • Ectromelia, Infectious / prevention & control*
  • Female
  • Gene Deletion*
  • Mice
  • Pregnancy
  • RNA-Binding Proteins / genetics*
  • Smallpox Vaccine / administration & dosage
  • Smallpox Vaccine / immunology*
  • Survival Analysis
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology*
  • Vaccinia virus / pathogenicity
  • Viral Proteins / genetics*
  • Viremia / prevention & control
  • Virulence Factors / genetics*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • E3L protein, Vaccinia virus
  • RNA-Binding Proteins
  • Smallpox Vaccine
  • Vaccines, Attenuated
  • Viral Proteins
  • Virulence Factors