title: Potent Functional Immunogenicity of Plasmodium falciparum Transmission-Blocking Antigen (Pfs25) Delivered with Nanoemulsion and Porous Polymeric Nanoparticles.
abstract: OBJECTIVE
  To evaluate functional immunogenicity of CHrPfs25. a malaria transmission blocking vaccine antigen, using nanoemulsion and porous polymeric PLGA nanoparticles.
  
  
  METHODS
  CHrPfs25 was formulated with nanoemulsions (NE) and poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) and evaluated via IM route in mice. Transmission blocking efficacy of antibodies was evaluated by standard mosquito membrane feeding assay using purified IgG from immune sera. Physicochemical properties and stability of various formulations were evaluated by measuring poly-dispersity index, particle size and zeta potential.
  
  
  RESULTS
  Mice immunized with CHrPfs25 using alum via IP and IM routes induced comparable immune responses. The highest antibody response was obtained with CHrPfs25 formulated in 4% NE as compared to 8% NE and PLGA-NP. No further increases were observed by combining NE with MPL-A and chitosan. One hundred percent transmission blocking activity was demonstrated at 400 μg/ml of IgG for alum groups (both routes IP and IM), 4% NE and NE-MPL-A. Purified IgG from various adjuvant groups at lower doses (100 μg/mL) still exhibited >90% transmission blocking activity, while 52-81% blocking was seen at 50 μg/mL.
  
  
  CONCLUSIONS
  Results suggest that CHrPfs25 delivered in various adjuvants/nanoparticles elicited strong functional immunogenicity in pre-clinical studies in mice. We are now continuing these studies to develop effective vaccine formulations for further evaluation of immune correlates of relative immunogenicity of CHrPfs25 in various adjuvants and clinical trials.
authors.affiliation: Department of Tropical Medicine and Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Center for Nanomedicine & Drug Delivery, Xavier University of Louisiana, New Orleans, Louisiana, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Ledet
authors.affiliation: Center for Nanomedicine & Drug Delivery, Xavier University of Louisiana, New Orleans, Louisiana, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Graves
authors.affiliation: Department of Tropical Medicine and Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, USA.
authors.forename: Dibyadyuti
authors.initials: D
authors.lastname: Datta
authors.affiliation: Center for Nanomedicine & Drug Delivery, Xavier University of Louisiana, New Orleans, Louisiana, USA.
authors.forename: Shana
authors.initials: S
authors.lastname: Robinson
authors.affiliation: Department of Tropical Medicine and Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, USA.
authors.forename: Geetha P
authors.initials: GP
authors.lastname: Bansal
authors.affiliation: Center for Nanomedicine & Drug Delivery, Xavier University of Louisiana, New Orleans, Louisiana, USA. tmandal@xula.edu.
authors.forename: Tarun
authors.initials: T
authors.lastname: Mandal
authors.affiliation: Department of Tropical Medicine and Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, USA. nkumar@tulane.edu.
authors.forename: Nirbhay
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004655:Emulsions / Q000737:chemistry; D005260:Female; D007114:Immunization; D019344:Lactic Acid / Q000737:chemistry*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000276:immunology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D004655:Emulsions; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C099774:transmission-Blocking Vaccine based on Pfs25; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA nanoparticles; malaria; nanoemulsion; vaccine