A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Nat Commun. 2018 Aug 3;9(1):3067. doi: 10.1038/s41467-018-05276-4.

Abstract

Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Genetic Vectors / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Polyproteins / genetics
  • Polyproteins / immunology*
  • Th17 Cells / metabolism
  • Th2 Cells / metabolism
  • Vaccination
  • Vaccines, Attenuated
  • Vaccines, DNA / immunology
  • Vaccines, Synthetic
  • Vesiculovirus / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*
  • Viral Nonstructural Proteins / metabolism*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Zika Virus / genetics
  • Zika Virus / immunology
  • Zika Virus / metabolism*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Cytokines
  • NS1 protein, zika virus
  • Polyproteins
  • Vaccines, Attenuated
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • Viral Vaccines
  • prM protein, Flavivirus