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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Veröffentlicht in:PLoS neglected tropical diseases 2020-02, Vol.14 (2), p.e0008027-e0008027
Hauptverfasser: Luo, Shengxue, Zhao, Wei, Ma, Xiaorui, Zhang, Panli, Liu, Bochao, Zhang, Ling, Wang, Wenjing, Wang, Yuanzhan, Fu, Yongshui, Allain, Jean-Pierre, Li, Tingting, Li, Chengyao
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container_title PLoS neglected tropical diseases
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creator Luo, Shengxue
Zhao, Wei
Ma, Xiaorui
Zhang, Panli
Liu, Bochao
Zhang, Ling
Wang, Wenjing
Wang, Yuanzhan
Fu, Yongshui
Allain, Jean-Pierre
Li, Tingting
Li, Chengyao
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 (103.66) 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
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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 (&lt;103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer &gt;103.66) and T-cell response (&gt;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&lt;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.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0008027</identifier><identifier>PMID: 32049958</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviridae Infections - immunology ; Adenoviridae Infections - veterinary ; Adenoviridae Infections - virology ; Adenoviruses ; Adenoviruses, Simian - classification ; Animals ; Antibodies ; Biology and life sciences ; Biopharmaceuticals ; Biotechnology ; Callithrix ; Complications ; Disease control ; Immunization ; Immunogenicity ; Infection ; Infections ; Inoculation ; Laboratories ; Lesions ; Low level ; Lymphocytes T ; Medicine ; Medicine and Health Sciences ; Mimicry ; Monkey Diseases - immunology ; Monkey Diseases - virology ; Neurological complications ; Novels ; Nucleic acids ; Peptides ; Primates ; Proteins ; Public health ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Saliva ; Spleen ; T cells ; Tropical diseases ; Vaccination ; Vaccines ; Vector-borne diseases ; Viremia ; Viruses ; Zika virus ; Zika Virus Infection - immunology ; Zika Virus Infection - veterinary ; γ-Interferon</subject><ispartof>PLoS neglected tropical diseases, 2020-02, Vol.14 (2), p.e0008027-e0008027</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. 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Zhao, Wei ; Ma, Xiaorui ; Zhang, Panli ; Liu, Bochao ; Zhang, Ling ; Wang, Wenjing ; Wang, Yuanzhan ; Fu, Yongshui ; Allain, Jean-Pierre ; Li, Tingting ; Li, Chengyao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-e34da508803446f81367a3c26ddb26e2bb0394bca6ba1d1355d6396cca546053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenoviridae Infections - immunology</topic><topic>Adenoviridae Infections - veterinary</topic><topic>Adenoviridae Infections - virology</topic><topic>Adenoviruses</topic><topic>Adenoviruses, Simian - classification</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biology and life sciences</topic><topic>Biopharmaceuticals</topic><topic>Biotechnology</topic><topic>Callithrix</topic><topic>Complications</topic><topic>Disease control</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Infection</topic><topic>Infections</topic><topic>Inoculation</topic><topic>Laboratories</topic><topic>Lesions</topic><topic>Low level</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mimicry</topic><topic>Monkey Diseases - immunology</topic><topic>Monkey Diseases - virology</topic><topic>Neurological complications</topic><topic>Novels</topic><topic>Nucleic acids</topic><topic>Peptides</topic><topic>Primates</topic><topic>Proteins</topic><topic>Public health</topic><topic>Research and Analysis Methods</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Saliva</topic><topic>Spleen</topic><topic>T cells</topic><topic>Tropical diseases</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vector-borne diseases</topic><topic>Viremia</topic><topic>Viruses</topic><topic>Zika virus</topic><topic>Zika Virus Infection - immunology</topic><topic>Zika Virus Infection - veterinary</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Shengxue</creatorcontrib><creatorcontrib>Zhao, Wei</creatorcontrib><creatorcontrib>Ma, Xiaorui</creatorcontrib><creatorcontrib>Zhang, Panli</creatorcontrib><creatorcontrib>Liu, Bochao</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Wang, Yuanzhan</creatorcontrib><creatorcontrib>Fu, Yongshui</creatorcontrib><creatorcontrib>Allain, Jean-Pierre</creatorcontrib><creatorcontrib>Li, Tingting</creatorcontrib><creatorcontrib>Li, Chengyao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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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 (&lt;103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer &gt;103.66) and T-cell response (&gt;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&lt;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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32049958</pmid><doi>10.1371/journal.pntd.0008027</doi><orcidid>https://orcid.org/0000-0001-5727-2179</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adenoviridae Infections - immunology
Adenoviridae Infections - veterinary
Adenoviridae Infections - virology
Adenoviruses
Adenoviruses, Simian - classification
Animals
Antibodies
Biology and life sciences
Biopharmaceuticals
Biotechnology
Callithrix
Complications
Disease control
Immunization
Immunogenicity
Infection
Infections
Inoculation
Laboratories
Lesions
Low level
Lymphocytes T
Medicine
Medicine and Health Sciences
Mimicry
Monkey Diseases - immunology
Monkey Diseases - virology
Neurological complications
Novels
Nucleic acids
Peptides
Primates
Proteins
Public health
Research and Analysis Methods
Ribonucleic acid
RNA
Saliva
Spleen
T cells
Tropical diseases
Vaccination
Vaccines
Vector-borne diseases
Viremia
Viruses
Zika virus
Zika Virus Infection - immunology
Zika Virus Infection - veterinary
γ-Interferon
title A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection
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