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Article: Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models

TitleImmunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models
Authors
Keywordsadenovirus
envelope
premembrane
vaccine
Zika
Issue Date2018
PublisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org
Citation
The Journal of Infectious Diseases, 2018, v. 218 n. 3, p. 365-377 How to Cite?
AbstractBackground. Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain. Methods. We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains. Results. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-alpha/beta receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Conclusions. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.
Persistent Identifierhttp://hdl.handle.net/10722/273967
ISSN
2017 Impact Factor: 5.186
2015 SCImago Journal Rankings: 4.000
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGuo, Q-
dc.contributor.authorChan, JFW-
dc.contributor.authorPoon, KM-
dc.contributor.authorWu, S-
dc.contributor.authorChan, CS-
dc.contributor.authorHou, L-
dc.contributor.authorYip, CY-
dc.contributor.authorRen, C-
dc.contributor.authorCai, J-
dc.contributor.authorZhao, M-
dc.contributor.authorZhang, J-
dc.contributor.authorSong, X-
dc.contributor.authorChan, KH-
dc.contributor.authorWang, B-
dc.contributor.authorKok, KH-
dc.contributor.authorWen, Y-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, W-
dc.date.accessioned2019-08-18T14:52:21Z-
dc.date.available2019-08-18T14:52:21Z-
dc.date.issued2018-
dc.identifier.citationThe Journal of Infectious Diseases, 2018, v. 218 n. 3, p. 365-377-
dc.identifier.issn0022-1899-
dc.identifier.urihttp://hdl.handle.net/10722/273967-
dc.description.abstractBackground. Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain. Methods. We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains. Results. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-alpha/beta receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Conclusions. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org-
dc.relation.ispartofThe Journal of Infectious Diseases-
dc.subjectadenovirus-
dc.subjectenvelope-
dc.subjectpremembrane-
dc.subjectvaccine-
dc.subjectZika-
dc.titleImmunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models-
dc.typeArticle-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailPoon, KM: vinpoon@hku.hk-
dc.identifier.emailChan, CS: cschan@hku.hk-
dc.identifier.emailYip, CY: yipcyril@hku.hk-
dc.identifier.emailCai, J: caijuice@hku.hk-
dc.identifier.emailZhang, J: zhangajx@hkucc.hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYip, CY=rp01721-
dc.identifier.authorityZhang, J=rp00413-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/infdis/jiy187-
dc.identifier.pmid29617816-
dc.identifier.scopuseid_2-s2.0-85050824697-
dc.identifier.hkuros301248-
dc.identifier.volume218-
dc.identifier.issue3-
dc.identifier.spage365-
dc.identifier.epage377-
dc.identifier.isiWOS:000439174200005-
dc.publisher.placeUnited States-

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