Superior protection provided by a single dose of MF59-adjuvanted whole inactivated H5N1 influenza vaccine in type 1 diabetic mice

Arch Virol. 2011 Mar;156(3):387-95. doi: 10.1007/s00705-010-0860-4. Epub 2010 Nov 26.

Abstract

Vaccination is the preferred strategy for the prevention of influenza virus infection. Both H5N1 subunit and split vaccines have shown poor immunogenicity in clinical trials thus far. Therefore, it is urgent to develop more immunogenic and antigen-sparing H5N1 influenza vaccines as well as safe and effective adjuvants for humans, especially for immunocompromised people such as patients with diabetes mellitus. In this study, the protective effect of an MF59-adjuvanted inactivated whole-virion H5N1 vaccine was investigated in a type 1 diabetic mouse model. Mice (both healthy and diabetic) were immunized with a single dose of the inactivated vaccine, alone or adjuvanted with MF59 or Al(OH)(3). After four weeks, mice were challenged with a lethal dose of H5N1 virus. Antibody responses, survival rates, lung virus titers and body weight changes were tested. The results showed that addition of MF59 or Al(OH)(3) to the vaccine enhanced the antibody responses in both healthy mice and diabetic mice, but the MF59-adjuvanted groups showed higher antibody responses than the Al(OH)(3)-adjuvanted groups. The addition of MF59 or Al(OH)(3) to the vaccine led to a conversion of the immune response from a Th1-biased response to an enhanced mixed Th1/Th2 profile. The MF59-adjuvanted inactivated whole-virion H5N1 vaccine provided superior protection in type 1 diabetic mice to either the vaccine alone or the vaccine adjuvanted with Al(OH)(3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Viral / blood
  • Body Weight
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Models, Animal
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Polysorbates / administration & dosage*
  • Squalene / administration & dosage*
  • Survival Analysis
  • Vaccination / methods*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Viral Load

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • MF59 oil emulsion
  • Polysorbates
  • Vaccines, Inactivated
  • Squalene