Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization
<p>Abstract</p> <p>The present study has evaluated the immunogenicity of single or multiple <it>Plasmodium falciparum (Pf) </it>antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with...
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Language: | English |
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BMC
2007-10-01
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Series: | Malaria Journal |
Online Access: | http://www.malariajournal.com/content/6/1/135 |
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author | Strobert Elizabeth Weiss Walter R Geall Andrew Patterson Noelle B Fallarme Victoria Ganeshan Harini Abot Steve Richie Nancy Banania Glenna Baraceros Maria F Moreno Alberto Charoenvit Yupin Jiang George Caro-Aquilar Ivette Lanar David E Saul Allan Martin Laura B Gowda Kalpana Morrissette Craig R Kaslow David C Carucci Daniel J Galinski Mary R Doolan Denise L |
author_facet | Strobert Elizabeth Weiss Walter R Geall Andrew Patterson Noelle B Fallarme Victoria Ganeshan Harini Abot Steve Richie Nancy Banania Glenna Baraceros Maria F Moreno Alberto Charoenvit Yupin Jiang George Caro-Aquilar Ivette Lanar David E Saul Allan Martin Laura B Gowda Kalpana Morrissette Craig R Kaslow David C Carucci Daniel J Galinski Mary R Doolan Denise L |
author_sort | Strobert Elizabeth |
collection | DOAJ |
description | <p>Abstract</p> <p>The present study has evaluated the immunogenicity of single or multiple <it>Plasmodium falciparum (Pf) </it>antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with <it>Pf</it>CSP plasmid DNA or a mixture of <it>Pf</it>CSP, <it>Pf</it>SSP2/TRAP, <it>Pf</it>LSA1, <it>Pf</it>AMA1 and <it>Pf</it>MSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-<it>Pf</it>7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-γ 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 <it>Pf</it>CSP 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-γ responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent <it>Pf </it>vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.</p> |
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spelling | doaj.art-e5647d5a43ae438b92fbc4fafd25557e2022-12-22T01:12:56ZengBMCMalaria Journal1475-28752007-10-016113510.1186/1475-2875-6-135Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunizationStrobert ElizabethWeiss Walter RGeall AndrewPatterson Noelle BFallarme VictoriaGaneshan HariniAbot SteveRichie NancyBanania GlennaBaraceros Maria FMoreno AlbertoCharoenvit YupinJiang GeorgeCaro-Aquilar IvetteLanar David ESaul AllanMartin Laura BGowda KalpanaMorrissette Craig RKaslow David CCarucci Daniel JGalinski Mary RDoolan Denise L<p>Abstract</p> <p>The present study has evaluated the immunogenicity of single or multiple <it>Plasmodium falciparum (Pf) </it>antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with <it>Pf</it>CSP plasmid DNA or a mixture of <it>Pf</it>CSP, <it>Pf</it>SSP2/TRAP, <it>Pf</it>LSA1, <it>Pf</it>AMA1 and <it>Pf</it>MSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-<it>Pf</it>7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-γ 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 <it>Pf</it>CSP 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-γ responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent <it>Pf </it>vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.</p>http://www.malariajournal.com/content/6/1/135 |
spellingShingle | Strobert Elizabeth Weiss Walter R Geall Andrew Patterson Noelle B Fallarme Victoria Ganeshan Harini Abot Steve Richie Nancy Banania Glenna Baraceros Maria F Moreno Alberto Charoenvit Yupin Jiang George Caro-Aquilar Ivette Lanar David E Saul Allan Martin Laura B Gowda Kalpana Morrissette Craig R Kaslow David C Carucci Daniel J Galinski Mary R Doolan Denise L Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization Malaria Journal |
title | Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization |
title_full | Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization |
title_fullStr | Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization |
title_full_unstemmed | Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization |
title_short | Induction of multi-antigen multi-stage immune responses against <it>Plasmodium falciparum </it>in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization |
title_sort | induction of multi antigen multi stage immune responses against it plasmodium falciparum it in rhesus monkeys in the absence of antigen interference with heterologous dna prime poxvirus boost immunization |
url | http://www.malariajournal.com/content/6/1/135 |
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