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

• 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

<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>