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

被引:67
作者
Prow, Natalie A. [1 ,2 ,3 ]
Liu, Liang [4 ]
Nakayama, Eri [1 ,5 ]
Cooper, Tamara H. [4 ]
Yan, Kexin [1 ]
Eldi, Preethi [4 ]
Hazlewood, Jessamine E. [1 ]
Tang, Bing [1 ]
Le, Thuy T. [1 ]
Setoh, Yin Xiang [6 ]
Khromykh, Alexander A. [2 ,3 ,6 ]
Hobson-Peters, Jody [6 ]
Diener, Kerrilyn R. [4 ,7 ,8 ]
Howley, Paul M. [9 ]
Hayball, John D. [4 ,7 ,8 ]
Suhrbier, Andreas [1 ,2 ,3 ]
机构
[1] QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia
[2] Australian Infect Dis Res Ctr, Brisbane, Qld 4029, Australia
[3] Australian Infect Dis Res Ctr, Brisbane, Qld 4072, Australia
[4] Univ South Australia, Inst Hlth Res, Sch Pharm & Med Sci, Expt Therapeut Lab, Adelaide, SA 5000, Australia
[5] Natl Inst Infect Dis, Dept Virol 1, Tokyo 1628640, Japan
[6] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia
[7] Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia
[8] Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia
[9] Sementis Ltd, Berwick, Vic 3806, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
HUMORAL IMMUNITY; IN-VIVO; INFECTION; CELL; VACCINATIONS; TRANSMISSION; RESPONSES; CAPACITY; STRAIN; DENGUE;
D O I
10.1038/s41467-018-03662-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus 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.
引用
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页数:12
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