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

Jiang, George, Charoenvit, Yupin, Moreno, Alberto, Baraceros, Maria F., Banania, Glenna, Richie, Nancy, Abot, Steve, Ganeshan, Harini, Fallarme, Victoria, Patterson, Noelle B., Geall, Andrew, Weiss, Walter R., Strobert, Elizabeth, 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., and Doolan, Denise L. (2007) 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. Malaria Journal, 6 (135). pp. 1-17.

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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.

Item ID: 42742
Item Type: Article (Research - C1)
ISSN: 1475-2875
Additional Information:

© Jiang et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: United States Army Medical Research and Materiel Command (USAMRMC), Naval Medical Research Centre (NMRC)
Projects and Grants: USAMRMC 61153NM458.S18.A024
Date Deposited: 24 Mar 2016 01:25
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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