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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2007-10-01
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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