Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study

• Published in: PloS one 2016-12, Vol.11 (12), p.e0167663-e0167663
• Main Authors: Dalzon, Bastien, Lebas, Célia, Jimenez, Gina, Gutjahr, Alice, Terrat, Céline, Exposito, Jean-Yves, Verrier, Bernard, Lethias, Claire
• Format: Article
• Language: English
• Subjects: Acids; AIDS Vaccines - chemistry; AIDS Vaccines - immunology; Animals; Antibodies; Antigens; Avidity; Bacteria; Binding sites; Biodegradability; Biodegradation; Biology and Life Sciences; Cell Adhesion - physiology; Cell culture; Cell Line, Tumor; Coating; Confocal; Confocal microscopy; Dendritic cells; Drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Engineering and Technology; Female; Fibronectin; Fibronectins - chemistry; Flow Cytometry; Fluorescence; Humans; Immune response (humoral); Integrin alpha5beta1 - chemistry; Ligands; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Microscopy; Microscopy, Confocal; Mutagenesis; Nanoparticles; Nanoparticles - chemistry; p24 Protein; Pathogens; Physical Sciences; Polyesters - chemistry; Polylactic acid; Prospective Studies; Proteins; Recombinant Proteins - chemistry; Research and Analysis Methods; Vaccination; Vaccine efficacy; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167663

Biodegradable polymeric nanoparticles are vehicles of choice for drug delivery and have the ability to encapsulate and present at their surface different molecules of interest. Among these bio-nanocarriers, poly(lactic acid) (PLA) nanoparticles have been used as adjuvant and vehicle for enhanced vaccine efficacy. In order to develop an approach to efficient vaccine delivery, we developed nanoparticles to target α5β1 positive cells. We first overproduced, in bacteria, human fibronectin FNIII9/10 recombinant proteins possessing an integrin α5β1 binding site, the RGDS sequence, or a mutated form of this site. After having confirmed the integrin binding properties of these recombinant proteins in cell culture assays, we were able to formulate PLA nanoparticles with these FNIII9/10 proteins at their surface. We then confirmed, by fluorescence and confocal microscopy, an enhanced cellular uptake by α5β1+ cells of RGDS-FNIII9/10 coated PLA nanoparticles, in comparison to KGES-FNIII9/10 coated or non-coated controls. As a first vaccination approach, we prepared PLA nanoparticles co-coated with p24 (an HIV antigen), and RGDS- or KGES-FNIII9/10 proteins, followed by subcutaneous vaccine administration, in mice. Although we did not detect improvements in the apparent humoral response to p24 antigen in the serum of RGDS/p24 nanoparticle-treated mice, the presence of the FNIII proteins increased significantly the avidity index of anti-p24 antibodies compared to p24-nanoparticle-injected control mice. Future developments of this innovative targeted vaccine are discussed.