Vesicular Stomatitis Virus and DNA Vaccines Expressing Zika Virus Nonstructural Protein 1 Induce Substantial but Not Sterilizing Protection against Zika Virus Infection
| Autor: | Zayed Attia, Mark E. Peeples, Anzhong Li, Pei Yong Shi, Xueya Liang, Jingyou Yu, Mijia Lu, Shan-Lu Liu, Thomas Z. Gao, Miaoge Xue, Chao Shan, Jianrong Li, Prosper N. Boyaka |
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| Rok vydání: | 2020 |
| Předmět: |
viruses
Immunology Viremia Receptor Interferon alpha-beta Cross Reactions Viral Nonstructural Proteins Antibodies Viral Microbiology Vesicular stomatitis Indiana virus Zika virus Dengue fever DNA vaccination Mice 03 medical and health sciences 0302 clinical medicine Virology Vaccines and Antiviral Agents Vaccines DNA medicine Animals Antibody-dependent enhancement 030212 general & internal medicine 030304 developmental biology Mice Knockout Mice Inbred BALB C 0303 health sciences biology Zika Virus Infection Immunogenicity virus diseases Viral Vaccines Zika Virus biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease Antibodies Neutralizing Disease Models Animal Flavivirus Vesicular stomatitis virus Insect Science Female Vesicular Stomatitis |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| Popis: | The nonstructural protein 1 (NS1) of several flaviviruses, including West Nile, dengue, and yellow fever viruses, is capable of inducing variable degrees of protection against flavivirus infection in animal models. However, the immunogenicity of NS1 protein of Zika virus (ZIKV) is less understood. Here, we determined the efficacy of ZIKV NS1-based vaccine candidates using two delivery platforms, methyltransferase-defective recombinant vesicular stomatitis virus (mtdVSV) and a DNA vaccine. We first show that expression of ZIKV NS1 could be significantly enhanced by optimizing the signal peptide. A single dose of mtdVSV-NS1-based vaccine or two doses of DNA vaccine induced high levels of NS1-specfic antibody and T cell immune responses but provided only partial protection against ZIKV viremia in BALB/c mice. In Ifnar1(−/−) mice, neither NS1-based vaccine provided protection against a lethal high dose (10(5) PFU) ZIKV challenge, but mtdVSV-NS1-based vaccine prevented deaths from a low dose (10(3) PFU) challenge, though they experienced viremia and body weight loss. We conclude that ZIKV NS1 alone conferred substantial, but not complete, protection against ZIKV infection. Nevertheless, these results highlight the value of ZIKV NS1 for vaccine development. IMPORTANCE Most Zika virus (ZIKV) vaccine research has focused on the E or prM-E proteins and the induction of high levels of neutralizing antibodies. However, these ZIKV neutralizing antibodies cross-react with other flaviviruses, which may aggravate the disease via an antibody-dependent enhancement (ADE) mechanism. ZIKV NS1 protein may be an alternative antigen for vaccine development, since antibodies to NS1 do not bind to the virion, thereby eliminating the risk of ADE. Here, we show that recombinant VSV and DNA vaccines expressing NS1, alone, confer partial protection against ZIKV infection in both immunocompetent and immunodeficient mice, highlighting the value of NS1 as a potential vaccine candidate. |
| Databáze: | OpenAIRE |
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