A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

• Published in: Nature communications Vol. 9; no. 1; pp. 3067 - 17
• Main Authors: Li, Anzhong, Yu, Jingyou, Lu, Mijia, Ma, Yuanmei, Attia, Zayed, Shan, Chao, Xue, Miaoge, Liang, Xueya, Craig, Kelsey, Makadiya, Nirajkumar, He, Jennifer J., Jennings, Ryan, Shi, Pei-Yong, Peeples, Mark E., Liu, Shan-Lu, Boyaka, Prosper N., Li, Jianrong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.08.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/109; 13/21; 13/31; 14/28; 38/1; 38/77; 38/88; 631/326/590/1867; 64/60; 692/699/255/2514; 82/80; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens, Viral - genetics; Antigens, Viral - immunology; Antigens, Viral - metabolism; Attenuation; Cytokines - metabolism; Disease Models, Animal; Female; Genetic Vectors - immunology; Helper cells; Humanities and Social Sciences; Immune response; Immune response (cell-mediated); Immune system; Immunization; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Inbred BALB C; multidisciplinary; Polyproteins - genetics; Polyproteins - immunology; Proteins; Science; Science (multidisciplinary); Stomatitis; Th17 Cells - metabolism; Th2 Cells - metabolism; Vaccination; Vaccines; Vaccines, Attenuated; Vaccines, DNA - immunology; Vaccines, Synthetic; Vector-borne diseases; 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; Viruses; Zika virus; Zika Virus - genetics; Zika Virus - immunology; Zika Virus - metabolism; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05276-4

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. Current Zika virus (ZIKV) subunit vaccine development largely focuses on prM and E proteins, and the role of NS1 for immune response and protection is unclear. Here, Li et al. develop an attenuated VSV-based vaccine expressing a ZIKV prM-E-NS1 polyprotein and characterize immune response and protection in mice.