Induction of specific humoral and cellular immune responses in a mouse model following gene fusion of HSP70C and Hantaan virus Gn and S0.7 in an adenoviral vector

PLoS One. 2014 Feb 4;9(2):e88183. doi: 10.1371/journal.pone.0088183. eCollection 2014.

Abstract

Heat shock proteins (HSPs) display adjuvant functions when given as fusion proteins to enhance vaccination efficiency. To evaluate enhanced potency of Hantaan virus (HTNV) glycoprotein (GP) and nucleocapsid protein (NP) immunogenicity by heat shock protein 70 (HSP70), a recombinant adenovirus rAd-GnS0.7-pCAG-HSP70C expression vector was developed by genetically linking the HSP70 C-terminal gene (HSP70 359-610 aa, HSP70C) to the Gn and 0.7 kb fragment of the NP (aa1-274-S0.7). C57BL/6 mice were immunized with these recombinant adenoviral vectors. A series of immunological assays determined the immunogenicity of the recombinant adenoviral vectors. The results showed that rAd-GnS0.7-pCAG-HSP70C induced a stronger humoral and cellular immune response than other recombinant adenoviruses (rAd-GnS0.7-pCAG and rAd-GnS0.7) and the HFRS vaccine control. Animal protection experiments showed that rAd-GnS0.7-pCAG-HSP70C was effective at protecting C57BL/6 mice from HTNV infection. The results of the immunological experiments showed that HSP70C lead to enhanced vaccine potency, and suggested significant potential in the development of genetically engineered vaccines against HTNV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology
  • Female
  • Gene Fusion / genetics
  • Gene Fusion / immunology
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / immunology*
  • Hantaan virus / genetics
  • Hantaan virus / immunology*
  • Immunity, Cellular / genetics
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / genetics
  • Immunity, Humoral / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins / genetics
  • Nucleocapsid Proteins / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Vaccination / methods
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Glycoproteins
  • HSP70 Heat-Shock Proteins
  • Nucleocapsid Proteins
  • Recombinant Fusion Proteins
  • Viral Proteins
  • Viral Vaccines

Grants and funding

This work was supported by the National Key Basic Research Program (973 Program) (No.2012CB518905), the Natural Science Foundation of China (No. 81001344 and No. 31070810). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.