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

• Published in: Malaria Journal
• 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 in Journal/Newspaper
• Language: English
• Published: BMC 2007
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-6-135; https://doaj.org/article/e5647d5a43ae438b92fbc4fafd25557e

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 Pf CSP plasmid DNA or a mixture of Pf CSP, Pf SSP2/TRAP, Pf LSA1, Pf AMA1 and Pf MSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC- Pf 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 Pf 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 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.