Adenoviral vector type 26 encoding Zika virus (ZIKV) M-Env antigen induces humoral and cellular immune responses and protects mice and nonhuman primates against ZIKV challenge

PLoS One. 2018 Aug 24;13(8):e0202820. doi: 10.1371/journal.pone.0202820. eCollection 2018.

Abstract

In 2015, there was a large outbreak of Zika virus (ZIKV) in Brazil. Despite its relatively mild impact on healthy adults, ZIKV infection during pregnancy has been associated with severe birth defects. Currently, there is no ZIKV vaccine available, but several vaccine candidates based on the ZIKV membrane (M) and envelope (Env) structural proteins showed promising results in preclinical and clinical studies. Here, the immunogenicity and protective efficacy of a non-replicating adenoviral vector type 26 (Ad26) that encodes the ZIKV M-Env antigens (Ad26.ZIKV.M-Env) was evaluated in mice and non-human primates (NHP). Ad26.ZIKV.M-Env induced strong and durable cellular and humoral immune responses in preclinical models. Humoral responses were characterized by Env-binding and ZIKV neutralizing antibody responses while cellular responses were characterized by ZIKV reactive CD4+ and CD8+ T cells. Importantly, a single immunization with a very low dose of 4x107 vp of Ad26.ZIKV.M-Env protected mice from ZIKV challenge. In NHP, a single immunization with a typical human dose of 1x1011 vp of Ad26.ZIKV.M-Env also induced Env-binding and ZIKV neutralizing antibodies and Env and M specific cellular immune responses that associated with complete protection against viremia from ZIKV challenge as measured in plasma and other body fluids. Together these data provide the rationale to progress the Ad26.ZIKV.M-Env candidate vaccine to clinical testing.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Genetic Vectors / metabolism
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Primates
  • Vaccination
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / metabolism
  • Zika Virus / metabolism
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / prevention & control
  • Zika Virus Infection / veterinary
  • Zika Virus Infection / virology

Substances

  • Antibodies, Neutralizing
  • Antigens, Viral
  • Viral Envelope Proteins
  • Viral Matrix Proteins
  • Interferon-gamma

Grant support

The authors received no specific funding for this work. Janssen Vaccines & Prevention B.V. provided support in the form of salaries for authors FC, LVDF, EVH, ES, JV, JT, BK, HS AND RZ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.