title: The NYCBH vaccinia virus deleted for the innate immune evasion gene, E3L, protects rabbits against lethal challenge by rabbitpox virus.
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.
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Denzler
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Rice
authors.forename: Amy L
authors.initials: AL
authors.lastname: MacNeill
authors.forename: Nobuko
authors.initials: N
authors.lastname: Fukushima
authors.forename: Scott F
authors.initials: SF
authors.lastname: Lindsey
authors.forename: Greg
authors.initials: G
authors.lastname: Wallace
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Burrage
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Brandi R
authors.initials: BR
authors.lastname: Manning
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Swetnam
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Gray
authors.forename: R W
authors.initials: RW
authors.lastname: Moyer
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D005334:Fever / Q000517:prevention & control; D017353:Gene Deletion; D009092:Mucous Membrane / Q000821:virology; D016601:RNA-Binding Proteins / Q000235:genetics*; D011817:Rabbits; D012376:Rodent Diseases / Q000276:immunology / Q000517:prevention & control*; D012867:Skin / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000401:mortality / Q000517:prevention & control / Q000662:veterinary*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines; D037521:Virulence Factors