Research
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
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* Corresponding author: Denise L Doolan Denise.Doolan@qimr.edu.au
1 Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA
2 Henry M. Jackson Foundation, Rockville, MD 20852, USA
3 Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
4 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA 30329, USA
5 Vical, Inc., San Diego, CA 92121, USA
6 Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA
7 Malaria Vaccine Development Branch, National Institute of Allergies and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
8 Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205-2179, USA
9 The Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, PO Royal Brisbane Hospital, Brisbane QLD 4029 Australia
Malaria Journal 2007, 6:135 doi:10.1186/1475-2875-6-135
Published: 9 October 2007Abstract
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-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 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-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.