Effect of AcHERV-GmCSF as an Influenza Virus Vaccine Adjuvant

PLoS One. 2015 Jun 19;10(6):e0129761. doi: 10.1371/journal.pone.0129761. eCollection 2015.

Abstract

Introduction: The first identification of swine-originated influenza A/CA/04/2009 (pH1N1) as the cause of an outbreak of human influenza accelerated efforts to develop vaccines to prevent and control influenza viruses. The current norm in many countries is to prepare influenza vaccines using cell-based or egg-based killed vaccines, but it is difficult to elicit a sufficient immune response using this approach. To improve immune responses, researchers have examined the use of cytokines as vaccine adjuvants, and extensively investigated their functions as chemoattractants of immune cells and boosters of vaccine-mediated protection. Here, we evaluated the effect of Granulocyte-macrophage Colony-Stimulating Factor (GmCSF) as an influenza vaccine adjuvant in BALB/c mice.

Method and results: Female BALB/c mice were immunized with killed vaccine together with a murine GmCSF gene delivered by human endogenous retrovirus (HERV) envelope coated baculovirus (1 × 10(7) FFU AcHERV-GmCSF, i.m.) and were compared with mice immunized with the killed vaccine alone. On day 14, immunized mice were challenged with 10 median lethal dose of mouse adapted pH1N1 virus. The vaccination together with GmCSF treatment exerted a strong adjuvant effect on humoral and cellular immune responses. In addition, the vaccinated mice together with GmCSF were fully protected against infection by the lethal influenza pH1N1 virus.

Conclusion: Thus, these results indicate that AcHERV-GmCSF is an effective molecular adjuvant that augments immune responses against influenza virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Baculoviridae*
  • Cell Line
  • Endogenous Retroviruses* / genetics
  • Female
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor* / genetics
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Mice
  • Orthomyxoviridae Infections / prevention & control
  • Recombinant Proteins
  • Viral Envelope Proteins* / genetics

Substances

  • Adjuvants, Immunologic
  • Influenza Vaccines
  • Recombinant Proteins
  • Viral Envelope Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor

Grants and funding

This work was supported by the National Agenda Project grant from Korea Research Council of Fundamental Science and Technology (NTM1311423) and the Korea Research Institute for Bioscience and Biotechnology (KRIBB) Initiative program (KGM3121423), by grants from the Korean Health Technology 3 R&D Project (No. A092010) and iPET(Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries) from Ministry of Agriculture, Food and Rural Affairs (112157-03-2-SB020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.