Different levels of immunogenicity of two strains of Fowlpox virus as recombinant vaccine vectors eliciting T-cell responses in heterologous prime-boost vaccination strategies.
The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.
Cottingham
Matthew G
MG
Department of Virology, Division of Investigative Science, Faculty of Medicine, Imperial College, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
van Maurik
Andre
A
Zago
Manola
M
Newton
Angela T
AT
Anderson
Richard J
RJ
Howard
M Keith
MK
Schneider
Jörg
J
Skinner
Michael A
MA
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000818:Animals; D005260:Female; D005587:Fowlpox virus / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D020815:Polyproteins / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D017780:Malaria Vaccines; D020815:Polyproteins; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma