title: 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.
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 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-gamma 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-gamma 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.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA. jiang_george@bah.com
authors.forename: George
authors.initials: G
authors.lastname: Jiang
authors.forename: Yupin
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: Alberto
authors.initials: A
authors.lastname: Moreno
authors.forename: Maria F
authors.initials: MF
authors.lastname: Baraceros
authors.forename: Glenna
authors.initials: G
authors.lastname: Banania
authors.forename: Nancy
authors.initials: N
authors.lastname: Richie
authors.forename: Steve
authors.initials: S
authors.lastname: Abot
authors.forename: Harini
authors.initials: H
authors.lastname: Ganeshan
authors.forename: Victoria
authors.initials: V
authors.lastname: Fallarme
authors.forename: Noelle B
authors.initials: NB
authors.lastname: Patterson
authors.forename: Andrew
authors.initials: A
authors.lastname: Geall
authors.forename: Walter R
authors.initials: WR
authors.lastname: Weiss
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Strobert
authors.forename: Ivette
authors.initials: I
authors.lastname: Caro-Aquilar
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gowda
authors.forename: Craig R
authors.initials: CR
authors.lastname: Morrissette
authors.forename: David C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carucci
authors.forename: Mary R
authors.initials: MR
authors.lastname: Galinski
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary / Q000379:methods*; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D010957:Plasmids; D010963:Plasmodium falciparum / Q000276:immunology*; D011212:Poxviridae / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D019444:Vaccines, DNA