Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.

Abstract

To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.

• Authors: Il Gyu Kong, Ayuko Sato, Yoshikazu Yuki, Tomonori Nochi, Haruko Takahashi, Shinichi Sawada, Mio Mejima, Shiho Kurokawa, Kazunari Okada, Shintaro Sato, David E Briles, Jun Kunisawa, Yusuke Inoue, Masafumi Yamamoto, Kazunari Akiyoshi, Hiroshi Kiyono
• Journal: Infection and immunity (Infect Immun) Vol. 81 Issue 5 Pg. 1625-34 (May 2013) ISSN: 1098-5522 [Electronic] United States
• PMID: 23460513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Proteins
• Immunoglobulin A
• Immunoglobulin G
• Nanogels
• Pneumococcal Vaccines
• pneumococcal surface protein A
• polyethylene glycol polyethyleneimine nanogel
• Polyethylene Glycols
• Polyethyleneimine

Topics

• Adaptive Immunity
• Administration, Intranasal
• Animals
• Antibodies, Bacterial (blood, immunology)
• Antigens, Bacterial (administration & dosage, immunology)
• Bacterial Proteins (administration & dosage, immunology)
• Disease Models, Animal
• Female
• Immunoglobulin A (metabolism)
• Immunoglobulin G (blood)
• Mice
• Mice, Inbred BALB C
• Nanogels
• Nose (microbiology)
• Pneumococcal Infections (immunology, microbiology, prevention & control)
• Pneumococcal Vaccines (administration & dosage, immunology)
• Polyethylene Glycols
• Polyethyleneimine
• Streptococcus pneumoniae (drug effects, immunology)
• Th17 Cells (immunology)
• Th2 Cells (immunology)