DNA vaccines in sheep: CTLA-4 mediated targeting and CpG motifs enhance immunogenicity in a DNA prime/protein boost strategy

Nicholas J. Kennedy, Terry Spithill, Jan Tennent, Paul R. Wood, David Piedrafita

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

DNA vaccines have proven to be an efficient means of inducing immune responses in small laboratory animals; however, their efficacy in large out-bred animal models has been much less promising. In addressing this issue, we have investigated the ability of ovine cytotoxic lymphocyte antigen 4 (CTLA-4) mediated targeting and ruminant specific CpG optimised plasmids, both alone and in combination, to enhance immune responses in sheep to the pro cathepsin B (FhCatB) antigen from Fasciola hepatica. In this study, CTLA-4 mediated targeting enhanced the speed and magnitude of the primary antibody response and effectively primed for a potent memory response compared to conventional DNA vaccination alone, which failed to induce a detectable immune response. While the CpG-augmentation of the CTLA-4 targeted construct did not further enhance the magnitude or isotype profile of the CTLA-4 induced antibody titres, it did result in the induction of significant antigen-specific, lymphocyte- proliferative responses that were not observed in any other treatment group, showing for the first time that significant cellular responses can be induced in sheep following DNA vaccination. In contrast, CpG-augmentation in the absence of CTLA-4 mediated targeting failed to induce a detectable immune response. This is the first study to explore the potential adjuvant effects of ruminant specific CpG motifs on DNA vaccine induced immune responses in sheep. The ability of CpG-augmented CTLA-4 mediated targeting to induce both humoral and cellular immune responses in this study suggests that this may be an effective approach for enhancing the efficacy of DNA vaccines in large out-bred animal models.
Original languageEnglish
Pages (from-to)970-979
Number of pages10
JournalVaccine
Volume24
Issue number7
DOIs
Publication statusPublished - 2006

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lymphocyte antigens
DNA Vaccines
recombinant vaccines
Sheep
immune response
Lymphocytes
Antigens
sheep
DNA
Proteins
proteins
Aptitude
ruminants
Ruminants
animal models
vaccination
antigens
breeds
cathepsin B
Vaccination

Cite this

Kennedy, Nicholas J. ; Spithill, Terry ; Tennent, Jan ; Wood, Paul R. ; Piedrafita, David. / DNA vaccines in sheep : CTLA-4 mediated targeting and CpG motifs enhance immunogenicity in a DNA prime/protein boost strategy. In: Vaccine. 2006 ; Vol. 24, No. 7. pp. 970-979.
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DNA vaccines in sheep : CTLA-4 mediated targeting and CpG motifs enhance immunogenicity in a DNA prime/protein boost strategy. / Kennedy, Nicholas J.; Spithill, Terry; Tennent, Jan; Wood, Paul R.; Piedrafita, David.

In: Vaccine, Vol. 24, No. 7, 2006, p. 970-979.

Research output: Contribution to journalArticle

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T2 - CTLA-4 mediated targeting and CpG motifs enhance immunogenicity in a DNA prime/protein boost strategy

AU - Kennedy, Nicholas J.

AU - Spithill, Terry

AU - Tennent, Jan

AU - Wood, Paul R.

AU - Piedrafita, David

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AB - DNA vaccines have proven to be an efficient means of inducing immune responses in small laboratory animals; however, their efficacy in large out-bred animal models has been much less promising. In addressing this issue, we have investigated the ability of ovine cytotoxic lymphocyte antigen 4 (CTLA-4) mediated targeting and ruminant specific CpG optimised plasmids, both alone and in combination, to enhance immune responses in sheep to the pro cathepsin B (FhCatB) antigen from Fasciola hepatica. In this study, CTLA-4 mediated targeting enhanced the speed and magnitude of the primary antibody response and effectively primed for a potent memory response compared to conventional DNA vaccination alone, which failed to induce a detectable immune response. While the CpG-augmentation of the CTLA-4 targeted construct did not further enhance the magnitude or isotype profile of the CTLA-4 induced antibody titres, it did result in the induction of significant antigen-specific, lymphocyte- proliferative responses that were not observed in any other treatment group, showing for the first time that significant cellular responses can be induced in sheep following DNA vaccination. In contrast, CpG-augmentation in the absence of CTLA-4 mediated targeting failed to induce a detectable immune response. This is the first study to explore the potential adjuvant effects of ruminant specific CpG motifs on DNA vaccine induced immune responses in sheep. The ability of CpG-augmented CTLA-4 mediated targeting to induce both humoral and cellular immune responses in this study suggests that this may be an effective approach for enhancing the efficacy of DNA vaccines in large out-bred animal models.

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KW - DNA vaccine

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