The NYCBH vaccinia virus deleted for the innate immune evasion gene, E3L, protects rabbits against lethal challenge by rabbitpox virus

Karen L. Denzler, Amanda D. Rice, Amy L. MacNeill, Nobuko Fukushima, Scott F. Lindsey, Greg Wallace, Andrew M. Burrage, Andrew J. Smith, Brandi R. Manning, Daniele M. Swetnam, Stacey A. Gray, R. W. Moyer, Bertram Jacobs

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Vaccinia virus deleted for the innate immune evasion gene, E3L, has been shown to be highly attenuated and yet induces a protective immune response against challenge by homologous virus in a mouse model. In this manuscript the NYCBH vaccinia virus vaccine strain was compared to NYCBH vaccinia virus deleted for E3L (NYCBHΔE3L) in a rabbitpox virus (RPV) challenge model. Upon scarification, both vaccines produced a desired skin lesion, although the lesion produced by NYCBHΔE3L was smaller. Both vaccines fully protected rabbits against lethal challenge by escalating doses of RPV, from 10LD 50 to 1000LD 50. A single dose of NYCBHΔE3L protected rabbits from weight loss, fever, and clinical symptoms following the lowest dose challenge of 10LD 50, however it allowed a moderate level of RPV replication at the challenge site, some spread to external skin and mucosal surfaces, and increased numbers of secondary lesions as compared to vaccination with NYCBH. Alternately, two doses of NYCBHΔE3L fully protected rabbits from weight loss, fever, and clinical symptoms, following challenge with 100-1000LD 50 RPV, and it prevented development of secondary lesions similar to protection seen with NYCBH. Finally, vaccination with either one or two doses of NYCBHΔE3L resulted in similar neutralizing antibody titers following RPV challenge as compared to titers obtained by vaccination with NYCBH. These results support the efficacy of the attenuated NYCBHΔE3L in protection against an orthologous poxvirus challenge.

Original languageEnglish (US)
Pages (from-to)7659-7669
Number of pages11
JournalVaccine
Volume29
Issue number44
DOIs
StatePublished - Oct 13 2011

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Keywords

  • E3L gene
  • Rabbitpox virus
  • Smallpox
  • Vaccinia virus

ASJC Scopus subject areas

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

Cite this

Denzler, K. L., Rice, A. D., MacNeill, A. L., Fukushima, N., Lindsey, S. F., Wallace, G., Burrage, A. M., Smith, A. J., Manning, B. R., Swetnam, D. M., Gray, S. A., Moyer, R. W., & Jacobs, B. (2011). The NYCBH vaccinia virus deleted for the innate immune evasion gene, E3L, protects rabbits against lethal challenge by rabbitpox virus. Vaccine, 29(44), 7659-7669. https://doi.org/10.1016/j.vaccine.2011.07.140