title: Enhancement of Sm-p80 (large subunit of calpain) induced protective immunity against Schistosoma mansoni through co-delivery of interleukin-2 and interleukin-12 in a DNA vaccine formulation.
abstract: Schistosomiasis afflicts an estimated 200 million people in 76 countries and an additional 600 million people are at risk of acquiring this infection. Even though effective anthelmintic treatment and snail eradication control programs exist, the discovery of an effective vaccine still remains the most potentially powerful means of control for this disease. We have concentrated on a vaccine candidate (large subunit of calpain or Sm-p80) because of its potential in conferring protection against challenge infection and its pivotal role in surface membrane biogenesis of schistosomes. Since surface membrane renewal is a major phenomenon employed by hemohelminths to evade host immune system; an immune response directed against Sm-p80 should make the parasite prone to immune clearance from the host by both providing a well-targeted attack and by potentially inhibiting the surface membrane biogenesis process. In the present study, we have utilized DNA immunization protocols using Sm-p80 with plasmids encoding interleukin-2 (IL-2) and interleukin-12 (IL-12). Sm-p80 by itself provided a 39% protection (P</=0.0001) against challenge infection in C57BL/6 mice. This protection was increased to 57% (P</=0.0001) when plasmid encoding IL-2 was co-administered with Sm-p80 DNA. Co-injection of plasmid DNA encoding IL-12 with Sm-p80 DNA yielded a protection level of 45% (P</=0.0001). Statistically, the protection conferred by including IL-2 and IL-12 was significantly greater than when only the Sm-p80 was used. Sm-p80 DNA by itself elicited strong responses that includes IgG(2A) and IgG(2B) antibody isotypes. The introduction of IL-2 DNA with Sm-p80 DNA led to an increase in total IgG and IgG(2A) and IgG(2B) titres. Whereas co-administration of IL-12 DNA with Sm-p80 DNA resulted in the augmentation of only total IgG and IgG(2A). This data reinforces the potential of Sm-p80 as an excellent candidate for a schistosomiasis vaccine.
authors.affiliation: Department of Internal Medicine, Texas Tech Woman's Health & Research Institute, Texas Tech University Health Sciences Center, 1400 Wallace Blvd., Amarillo, Amarillo, TX 79106-1791, USA. siddiqui@ama.ttuhsc.edu
authors.forename: Afzal A
authors.initials: AA
authors.lastname: Siddiqui
authors.forename: Troy
authors.initials: T
authors.lastname: Phillips
authors.forename: Hugues
authors.initials: H
authors.lastname: Charest
authors.forename: Ron B
authors.initials: RB
authors.lastname: Podesta
authors.forename: Martha L
authors.initials: ML
authors.lastname: Quinlin
authors.forename: Justin R
authors.initials: JR
authors.lastname: Pinkston
authors.forename: Jenny D
authors.initials: JD
authors.lastname: Lloyd
authors.forename: Janet
authors.initials: J
authors.lastname: Pompa
authors.forename: Rachael M
authors.initials: RM
authors.lastname: Villalovos
authors.forename: Michelle
authors.initials: M
authors.lastname: Paz
mesh_terms: D000818:Animals; D016466:CHO Cells; D002154:Calpain / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007273:Injections, Intramuscular; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D021122:Protein Subunits; D019444:Vaccines, DNA; D018664:Interleukin-12; D002154:Calpain