Recombinant DNA vaccine of Hantavirus Gn and LAMP1 induced long-term immune protection in mice

Antiviral Res. 2017 Feb:138:32-39. doi: 10.1016/j.antiviral.2016.12.001. Epub 2016 Dec 5.

Abstract

Background: Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations.

Methods & results: Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay. HTNV-challenge assay identified long-term protection. Safety was confirmed by histological and behavioral analysis. Epitope-spreading phenomenon was noted, revealing two sets of dominant T-cell epitopes cross-species.

Conclusion: pVAX-LAMP/Gn established memory responses within a long-term protection. Lysosome-targeted strategy showed promise on Gn-based DNA vaccine and further investigations are warranted in other immunogenic Hantaviral antigens.

Keywords: DNA vaccine; Glycoprotein N-terminal; Hantavirus; Lysosome-associated membrane protein; Memory immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • DNA
  • DNA, Recombinant / immunology
  • Enzyme-Linked Immunospot Assay
  • Hantavirus Infections / prevention & control*
  • Immunologic Memory*
  • Lysosomal Membrane Proteins / genetics*
  • Lysosomal Membrane Proteins / immunology
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Orthohantavirus / chemistry
  • Orthohantavirus / genetics
  • Orthohantavirus / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Viral Proteins / administration & dosage
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • DNA, Recombinant
  • Lamp1 protein, mouse
  • Lysosomal Membrane Proteins
  • Membrane Glycoproteins
  • Vaccines, DNA
  • Viral Proteins
  • Viral Vaccines
  • DNA