Characterization of a Species E Adenovirus Vector as a Zika virus vaccine

Sci Rep. 2020 Feb 27;10(1):3613. doi: 10.1038/s41598-020-60238-5.

Abstract

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize the T-cell biased immune response observed in Ad4 immunized mice. Vaccination of BALB/c mice resulted in immune correlates similar to C57BL/6 mice, confirming that this response is not mouse strain-specific. Vaccination with an Ad4 expressing an influenza hemagglutinin (HA) protein resulted in anti-HA T-cell responses without the development of significant anti-HA antibodies, indicating this unique response is specific to the Ad4 serotype rather than the transgene expressed. Co-administration of a UV inactivated Ad4 vector with the Ad5-prM-E vaccine led to a significant reduction in anti-ZIKV antibody development suggesting that this serotype-specific immune profile is capsid-dependent. These results highlight the serotype-specific immune profiles elicited by different Adenovirus vector types and emphasize the importance of continued characterization of these alternative Ad serotypes.

Publication types

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

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Female
  • Gene Expression
  • Genetic Vectors / genetics*
  • Genetic Vectors / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Vaccination
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Envelope Proteins
  • Viral Vaccines