Influenza hemagglutinin vaccine with poly(gamma-glutamic acid) nanoparticles enhances the protection against influenza virus infection through both humoral and cell-mediated immunity.

Abstract

Subcutaneous immunization with an influenza hemagglutinin (HA) vaccine can induce the production of virus-neutralizing antibodies, but not a cell-mediated immune response. Here we tested whether amphiphilic poly(gamma-glutamic acid)-graft-l-phenylalanine copolymers (gamma-PGA-NPs), which are derived from a bacterial capsular exopolymer produced by certain Bacillus natto strains, were an effective adjuvant for systemic influenza HA vaccination. Subcutaneous immunization with a mixture of HA vaccine and gamma-PGA-NPs induced higher mononuclear cell proliferation and the production of gamma-interferon (IFN-gamma), interleukin (IL)-4, and IL-6 upon HA restimulation, and enhanced not only anti-HA neutralizing antibody production but also the influenza virus-specific cell-mediated immune response, including CTL activity, compared with immunization with HA alone or a mixture of HA and aluminum adjuvant. HA vaccine with gamma-PGA-NPs protected mice against challenges with lethal doses of homologous influenza virus. The results indicate that adding gamma-PGA-NPs to the HA vaccine promotes effective protection and identifies gamma-PGA-NPs as a new, effective, and potent candidate adjuvant for a subcutaneous influenza virus vaccine.

• Authors: Shigefumi Okamoto, Hironori Yoshii, Takami Akagi, Mitsuru Akashi, Toyokazu Ishikawa, Yoshinobu Okuno, Michiaki Takahashi, Koichi Yamanishi, Yasuko Mori
• Journal: Vaccine (Vaccine) Vol. 25 Issue 49 Pg. 8270-8 (Nov 28 2007) ISSN: 0264-410X [Print] Netherlands
• PMID: 17977633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Viral
• Hemagglutinin Glycoproteins, Influenza Virus
• Influenza Vaccines
• Polyglutamic Acid
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antibodies, Viral (blood)
• Female
• Hemagglutinin Glycoproteins, Influenza Virus (immunology)
• Immunization
• Influenza A virus (immunology)
• Influenza Vaccines (administration & dosage, immunology)
• Interferon-gamma (biosynthesis)
• Leukocytes, Mononuclear (immunology)
• Lymphocyte Activation (immunology)
• Mice
• Nanoparticles (administration & dosage)
• Neutralization Tests
• Orthomyxoviridae Infections (immunology, prevention & control)
• Polyglutamic Acid (administration & dosage, immunology)
• T-Lymphocytes, Cytotoxic (immunology)