A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine exp...

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Main Authors: Shengxue Luo, Wei Zhao, Xiaorui Ma, Panli Zhang, Bochao Liu, Ling Zhang, Wenjing Wang, Yuanzhan Wang, Yongshui Fu, Jean-Pierre Allain, Tingting Li, Chengyao Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-02-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0008027
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author Shengxue Luo
Wei Zhao
Xiaorui Ma
Panli Zhang
Bochao Liu
Ling Zhang
Wenjing Wang
Yuanzhan Wang
Yongshui Fu
Jean-Pierre Allain
Tingting Li
Chengyao Li
author_facet Shengxue Luo
Wei Zhao
Xiaorui Ma
Panli Zhang
Bochao Liu
Ling Zhang
Wenjing Wang
Yuanzhan Wang
Yongshui Fu
Jean-Pierre Allain
Tingting Li
Chengyao Li
author_sort Shengxue Luo
collection DOAJ
description Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.
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spelling doaj.art-afb36d0bed1242518ac9f8ca33dd83132022-12-21T22:39:38ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-02-01142e000802710.1371/journal.pntd.0008027A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.Shengxue LuoWei ZhaoXiaorui MaPanli ZhangBochao LiuLing ZhangWenjing WangYuanzhan WangYongshui FuJean-Pierre AllainTingting LiChengyao LiZika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.https://doi.org/10.1371/journal.pntd.0008027
spellingShingle Shengxue Luo
Wei Zhao
Xiaorui Ma
Panli Zhang
Bochao Liu
Ling Zhang
Wenjing Wang
Yuanzhan Wang
Yongshui Fu
Jean-Pierre Allain
Tingting Li
Chengyao Li
A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
PLoS Neglected Tropical Diseases
title A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
title_full A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
title_fullStr A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
title_full_unstemmed A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
title_short A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.
title_sort high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against zika virus infection
url https://doi.org/10.1371/journal.pntd.0008027
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