A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses

• Published in: Nature communications Vol. 9; no. 1; pp. 1230 - 12
• Main Authors: Prow, Natalie A., Liu, Liang, Nakayama, Eri, Cooper, Tamara H., Yan, Kexin, Eldi, Preethi, Hazlewood, Jessamine E., Tang, Bing, Le, Thuy T., Setoh, Yin Xiang, Khromykh, Alexander A, Hobson-Peters, Jody, Diener, Kerrilyn R., Howley, Paul M., Hayball, John D., Suhrbier, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.03.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 14/63; 45/77; 631/326/590; 631/326/596/1282; 631/326/596/1746; 692/308/1426; 82/1; 82/29; 96/106; Animals; Antibodies; Antibodies, Neutralizing - biosynthesis; Aquatic insects; Arthritis; Cassettes; Cercopithecus aethiops; Chikungunya Fever - immunology; Chikungunya Fever - prevention & control; Chikungunya virus; Chikungunya virus - immunology; CHO Cells; Cricetulus; Disease transmission; Enzyme-Linked Immunosorbent Assay; Epidemics; Female; Fetuses; Flavivirus; Genetic Vectors; HeLa Cells; Humanities and Social Sciences; Humans; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; Mosquitoes; multidisciplinary; Pathogens; Placenta; Polyproteins; Pregnancy; Receptor, Interferon alpha-beta - genetics; Science; Science (multidisciplinary); Testes; Vaccination; Vaccines; Vaccinia; Vaccinia virus - genetics; Vector-borne diseases; Vero Cells; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Viremia; Viruses; Zika virus; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03662-6

Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictu s mosquitoes. The “Sementis Copenhagen Vector” (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. A single vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR −/− mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR −/− mice, and (iii) Zika virus viremia and testes infection and pathology in male IFNAR −/− mice. To our knowledge this represents the first single-vector construct, multi-pathogen vaccine encoding large polyproteins, and offers both simplified manufacturing and formulation, and reduced “shot burden” for these often co-circulating arboviruses. Zika and chikungunya virus are co-circulating in many regions and currently there is no approved vaccine for either virus. Here, the authors engineer one vaccinia virus based vaccine for both, Zika and chikungunya, and show protection from infection and pathogenesis in mice.