Humoral and cellular immunity against both ZIKV and poxvirus is elicited by a two-dose regimen using DNA and non-replicating vaccinia virus-based vaccine candidates

• Published in: Vaccine 2019-04, Vol.37 (15), p.2122-2130
• Main Authors: Zhan, Ying, Deng, Yao, Huang, Baoying, Song, Qianqian, Wang, Wen, Yang, Yang, Dai, Lianpan, Wang, Wenling, Yan, Jinghua, Gao, Gorge F., Tan, Wenjie
• Format: Article
• Language: English
• Subjects: Antibodies; Candidates; CD8 antigen; Cell-mediated immunity; Clinical trials; Deoxyribonucleic acid; DNA; DNA vaccines; Epitopes; Glycoproteins; Guillain-Barre syndrome; Histocompatibility antigen H-2; Homology; Humoral immunity; Immune response; Immune system; Immunity; Immunization; Immunoglobulin G; Immunoglobulins; Infections; Laboratory animals; Lymphocytes; Lymphocytes T; Mice; Microcephaly; Neutralizing; Non-replicating vaccinia virus; Poxvirus; Prime-boost; Proteins; Public health; Recombinant DNA; Replication; Smallpox; T-cell epitope; Vaccine; Vaccines; Vector-borne diseases; Viral envelope proteins; Viruses; Zika virus; Zoonoses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.02.063

•We report a novel recombinant bivalent vaccine against ZIKV and orthopoxvirus.•We construct either DNA- or NTV-based vaccine expressing structural protein of ZIKV.•Immunity against ZIKV and poxvirus were detected in mice using this bivalent vaccine.•A significantly higher level of E-specific T cell responses was elicited in mice with prime-boost protocol.•A novel H-2d-restricted CD8 T-cell epitope was identified in ZIKV E protein. The Zika virus (ZIKV) and poxvirus infection are considered as public health emergencies, necessitating the development of effective vaccines. Here, we report novel recombinant DNA-based and non-replicating vaccinia virus (NTV)-based vaccine candidates that express the precursor membrane-envelope (prME) or envelope (E) glycoproteins of ZIKV. After immunization of BABL/c mice with the vaccines using a homologous protocol (DNA/DNA, NTV/NTV) or heterogeneous (DNA/NTV) protocol, a similar level of anti-E IgG and neutralizing antibodies (microneutralization test) were detected in the mice. However, a significantly higher level of E-specific T cell responses was elicited in mice when a heterogeneous prime-boost protocol was used (DNA/NTV) with either the DNA-based or NTV-based vaccines. Furthermore, neutralizing antibodies and a T cell immune response against the vaccinia virus (VV) were detected in mice that were subjected to the prime-boost protocol (DNA/NTV), whereas those subjected to a homologous NTV/NTV protocol had higher levels of anti-VV IgG and neutralizing antibodies. Lastly, a novel H-2d-restricted CD8 T-cell epitope, VRSYCYEASISDMAS, was identified in the ZIKV E protein. These data demonstrate proof of concept of a bivalent vaccine candidate against ZIKV and orthopoxvirus, and support the use of DNA-prME prime and NTV-E boost protocols to protect against ZIKV and orthopoxvirus infections.