Prime-boost vaccinations using recombinant flavivirus replicon and vaccinia virus vaccines: An ELISPOT analysis

Rattanasena, Paweena, Anraku, Itaru, Gardner, Joy, Le, Thuy T., Wang, Xiang Ju, Khromykh, Alexander A. and Suhrbier, Andreas (2011) Prime-boost vaccinations using recombinant flavivirus replicon and vaccinia virus vaccines: An ELISPOT analysis. Immunology and Cell Biology, 89 3: 426-436. doi:10.1038/icb.2010.99


Author Rattanasena, Paweena
Anraku, Itaru
Gardner, Joy
Le, Thuy T.
Wang, Xiang Ju
Khromykh, Alexander A.
Suhrbier, Andreas
Title Prime-boost vaccinations using recombinant flavivirus replicon and vaccinia virus vaccines: An ELISPOT analysis
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
1440-1711
Publication date 2011
Year available 2011
Sub-type Article (original research)
DOI 10.1038/icb.2010.99
Volume 89
Issue 3
Start page 426
End page 436
Total pages 11
Publisher Nature Publishing Group
Collection year 2012
Language eng
Subject 2403 Immunology
1307 Cell Biology
Abstract Recombinant Kunjin replicon virus-like particle (VLP), vaccinia virus (rVV) and DNA vaccines were tested in a large series of prime-boost vaccinations using interferon (IFN)γ ELISPOT assays that reflected effector (E), effector memory (EM) and central memory (CM) responses. All vaccine constructs encoded the murine polytope immunogen and responses to four CD8 T-cell epitopes (TYQRTRALV, SYIPSAEKI, YPHFMPTNL and RPQASGVYM) were measured. VLP/rVV out performed (by 14-to 20-fold) DNA/rVV for induction of CM responses, whereas EM responses were only marginally increased. DNA/VLP induced more EM, but not CM responses, than VLP alone, illustrating that DNA priming is not universally beneficial. rVV/VLP gave comparable results to VLP/rVV combinations, although the former induced approximately threefold more E responses, illustrating the utility of poxvirus priming in this setting. Although higher doses of VLP and rVV increased responses after single immunizations, such dose increases provided only marginal benefit in heterologous prime-boost settings. Triple combinations also provided no benefit over two vaccinations. DNA vaccination was associated with broad CM, but not EM responses, and the breadth of EM and E responses was significantly improved by increasing viral vector dose. VLP/rVV, rather than DNA priming, induced T cells with consistently high IFNγ secretion profiles across all ELISPOT measures. Vector-specific CD8 T-cell responses generally correlated well with immunogen-specific responses, although, as expected, single use of each vector reduced the relative levels of vector-specific responses. These experiments illustrate the utility of replicons in heterologous prime-boost vaccinations, and illustrate the diversity of data that can be obtained from ELISPOT analyses.
Keyword ELISPOT
Prime Boost Immunization
Replicon
Vaccinia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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