Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

Vaccine. 2011 Feb 1;29(6):1248-57. doi: 10.1016/j.vaccine.2010.11.079. Epub 2010 Dec 8.

Abstract

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Drug Carriers*
  • Female
  • Genetic Vectors*
  • Guinea Pigs
  • Lassa Fever / prevention & control*
  • Mice
  • Mice, Inbred CBA
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Yellow Fever Vaccine / genetics*
  • Yellow Fever Vaccine / immunology*

Substances

  • Drug Carriers
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Yellow Fever Vaccine
  • glycoprotein gp1, lassa virus
  • glycoprotein gp2, lassa virus