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Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization.

Jiang G, Charoenvit Y, Moreno A, Baraceros MF, Banania G, Richie N, Abot S, Ganeshan H, Fallarme V, Patterson NB, Geall A, Weiss WR, Strobert E, Caro-Aquilar I, Lanar DE, Saul A, Martin LB, Gowda K, Morrissette CR, Kaslow DC, Carucci DJ, Galinski MR, Doolan DL - Malar. J. (2007)

Bottom Line: Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone.CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost.Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

View Article: PubMed Central - HTML - PubMed

Affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA. jiang_george@bah.com

ABSTRACT
The present study has evaluated the immunogenicity of single or multiple Plasmodium falciparum (Pf) antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with PfCSP plasmid DNA or a mixture of PfCSP, PfSSP2/TRAP, PfLSA1, PfAMA1 and PfMSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-Pf7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-gamma ELIspot and intracellular cytokine staining, using recombinant proteins and overlapping synthetic peptides. Antigen-specific and parasite-specific antibody responses were evaluated by ELISA and IFAT, respectively. Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone. These data support the down-selection of the CSLAM antigen combination. CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost. In high responder monkeys, CD4+IL-2+ responses were more predominant than CD8+ T cell responses. Furthermore, CD8+ IFN-gamma responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

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Related in: MedlinePlus

Magnitude of PfCSP-specific IFN-γ responses from PfCSP/PBS and CSLAM/PBS immunized animals. PBMC were collected at time points as defined in the legend to Figure 2 and assayed against recombinant PfCSP protein by IFN-γ ELIspot. Results show the magnitude of SFC from individual monkeys immunized with either (A) PfCSP/PBS or (B) CSLAM/PBS.
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Figure 3: Magnitude of PfCSP-specific IFN-γ responses from PfCSP/PBS and CSLAM/PBS immunized animals. PBMC were collected at time points as defined in the legend to Figure 2 and assayed against recombinant PfCSP protein by IFN-γ ELIspot. Results show the magnitude of SFC from individual monkeys immunized with either (A) PfCSP/PBS or (B) CSLAM/PBS.

Mentions: Similarly, there was no significant difference in the magnitude of PfCSP-specific IFN-γ ELIspot responses between the PfCSP/PBS and CSLAM/PBS groups (Figure 3). At four weeks post 3rd DNA immunization, the SFC/million in responders to recombinant PfCSP protein ranged between 145 and 401 SFC/million (mean 269 SFC/million PBMC) for the CSLAM/PBS group as compared with a range of 40–102 SFC/million (average 71 SFC/million) for the PfCSP/PBS group. At 4 wks post viral boost, the magnitude of IFN-γ ELIspot forming cells was 246 SFC/million (range 51–466 SFC/million PBMC) for the CSLAM/PBS group versus 284 SFC/million (range 162–406 SFC/million PBMC) for the PfCSP/PBS group.


Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization.

Jiang G, Charoenvit Y, Moreno A, Baraceros MF, Banania G, Richie N, Abot S, Ganeshan H, Fallarme V, Patterson NB, Geall A, Weiss WR, Strobert E, Caro-Aquilar I, Lanar DE, Saul A, Martin LB, Gowda K, Morrissette CR, Kaslow DC, Carucci DJ, Galinski MR, Doolan DL - Malar. J. (2007)

Magnitude of PfCSP-specific IFN-γ responses from PfCSP/PBS and CSLAM/PBS immunized animals. PBMC were collected at time points as defined in the legend to Figure 2 and assayed against recombinant PfCSP protein by IFN-γ ELIspot. Results show the magnitude of SFC from individual monkeys immunized with either (A) PfCSP/PBS or (B) CSLAM/PBS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2147027&req=5

Figure 3: Magnitude of PfCSP-specific IFN-γ responses from PfCSP/PBS and CSLAM/PBS immunized animals. PBMC were collected at time points as defined in the legend to Figure 2 and assayed against recombinant PfCSP protein by IFN-γ ELIspot. Results show the magnitude of SFC from individual monkeys immunized with either (A) PfCSP/PBS or (B) CSLAM/PBS.
Mentions: Similarly, there was no significant difference in the magnitude of PfCSP-specific IFN-γ ELIspot responses between the PfCSP/PBS and CSLAM/PBS groups (Figure 3). At four weeks post 3rd DNA immunization, the SFC/million in responders to recombinant PfCSP protein ranged between 145 and 401 SFC/million (mean 269 SFC/million PBMC) for the CSLAM/PBS group as compared with a range of 40–102 SFC/million (average 71 SFC/million) for the PfCSP/PBS group. At 4 wks post viral boost, the magnitude of IFN-γ ELIspot forming cells was 246 SFC/million (range 51–466 SFC/million PBMC) for the CSLAM/PBS group versus 284 SFC/million (range 162–406 SFC/million PBMC) for the PfCSP/PBS group.

Bottom Line: Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone.CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost.Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

View Article: PubMed Central - HTML - PubMed

Affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA. jiang_george@bah.com

ABSTRACT
The present study has evaluated the immunogenicity of single or multiple Plasmodium falciparum (Pf) antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with PfCSP plasmid DNA or a mixture of PfCSP, PfSSP2/TRAP, PfLSA1, PfAMA1 and PfMSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-Pf7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-gamma ELIspot and intracellular cytokine staining, using recombinant proteins and overlapping synthetic peptides. Antigen-specific and parasite-specific antibody responses were evaluated by ELISA and IFAT, respectively. Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone. These data support the down-selection of the CSLAM antigen combination. CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost. In high responder monkeys, CD4+IL-2+ responses were more predominant than CD8+ T cell responses. Furthermore, CD8+ IFN-gamma responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

Show MeSH
Related in: MedlinePlus