Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid.

Julie L. Boyer, Carolina Sofer-Podesta, John Ang, Neil R. Hackett, Maria J. Chiuchiolo, Svetlana Senina, David Perlin, Ronald Crystal

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The aerosol form of the bacterium Yersinia pestis causes pneumonic plague, a rapidly fatal disease that is a biothreat if deliberately released. At present, no plague vaccines are available for use in the United States, but subunit vaccines based on the Y. pestis V antigen and F1 capsular protein show promise when administered with adjuvants. In the context that adenovirus (Ad) gene transfer vectors have a strong adjuvant potential related to the ability to directly infect dendritic cells, we hypothesized that modification of the Ad5 capsid to display either the Y. pestis V antigen or the F1 capsular antigen on the virion surface would elicit high V antigen- or F1-specific antibody titers, permit boosting with the same Ad serotype, and provide better protection against a lethal Y. pestis challenge than immunization with equivalent amounts of V or F1 recombinant protein plus conventional adjuvant. We constructed AdYFP-pIX/V and AdLacZ-pIX/F1, E1(-), E3(-) serotype 5 Ad gene transfer vectors containing a fusion of the sequence for either the Y. pestis V antigen or the F1 capsular antigen to the carboxy-terminal sequence of pIX, a capsid protein that can accommodate the entire V antigen (37 kDa) or F1 protein (15 kDa) without disturbing Ad function. Immunization with AdYFP-pIX/V followed by a single repeat administration of the same vector at the same dose resulted in significantly better protection of immunized animals compared with immunization with a molar equivalent amount of purified recombinant V antigen plus Alhydrogel adjuvant. Similarly, immunization with AdLacZ-pIX/F1 in a prime-boost regimen resulted in significantly enhanced protection of immunized animals compared with immunization with a molar-equivalent amount of purified recombinant F1 protein plus adjuvant. These observations demonstrate that Ad vaccine vectors containing pathogen-specific antigens fused to the pIX capsid protein have strong adjuvant properties and stimulate more robust protective immune responses than equivalent recombinant protein-based subunit vaccines administered with conventional adjuvant, suggesting that F1-and/or V-modified capsid Ad-based recombinant vaccines should be considered for development as anti-plague vaccines.

Original languageEnglish
Pages (from-to)891-901
Number of pages11
JournalHuman Gene Therapy
Volume21
Issue number7
Publication statusPublished - 1 Jul 2010
Externally publishedYes

Fingerprint

Yersinia pestis
Capsid
Adenoviridae
Immunity
Antigens
Immunization
Plague Vaccine
Recombinant Proteins
Subunit Vaccines
Capsid Proteins
Adenovirus Vaccines
Aluminum Hydroxide
Synthetic Vaccines
Plague
Protein Subunits
Aerosols
Virion
Dendritic Cells
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid. / Boyer, Julie L.; Sofer-Podesta, Carolina; Ang, John; Hackett, Neil R.; Chiuchiolo, Maria J.; Senina, Svetlana; Perlin, David; Crystal, Ronald.

In: Human Gene Therapy, Vol. 21, No. 7, 01.07.2010, p. 891-901.

Research output: Contribution to journalArticle

Boyer, JL, Sofer-Podesta, C, Ang, J, Hackett, NR, Chiuchiolo, MJ, Senina, S, Perlin, D & Crystal, R 2010, 'Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid.', Human Gene Therapy, vol. 21, no. 7, pp. 891-901.
Boyer, Julie L. ; Sofer-Podesta, Carolina ; Ang, John ; Hackett, Neil R. ; Chiuchiolo, Maria J. ; Senina, Svetlana ; Perlin, David ; Crystal, Ronald. / Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid. In: Human Gene Therapy. 2010 ; Vol. 21, No. 7. pp. 891-901.
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