An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model
Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines ar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/3/112 |
| _version_ | 1798005133276086272 |
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| author | Arun S. Annamalai Aryamav Pattnaik Bikash R. Sahoo Zack P. Guinn Brianna L. Bullard Eric A. Weaver David Steffen Sathish Kumar Natarajan Thomas M. Petro Asit K. Pattnaik |
| author_facet | Arun S. Annamalai Aryamav Pattnaik Bikash R. Sahoo Zack P. Guinn Brianna L. Bullard Eric A. Weaver David Steffen Sathish Kumar Natarajan Thomas M. Petro Asit K. Pattnaik |
| author_sort | Arun S. Annamalai |
| collection | DOAJ |
| description | Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate. |
| first_indexed | 2024-04-11T12:35:24Z |
| format | Article |
| id | doaj.art-4e929973e4d44af28f80547866d43e72 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T12:35:24Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-4e929973e4d44af28f80547866d43e722022-12-22T04:23:39ZengMDPI AGVaccines2076-393X2019-09-017311210.3390/vaccines7030112vaccines7030112An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse ModelArun S. Annamalai0Aryamav Pattnaik1Bikash R. Sahoo2Zack P. Guinn3Brianna L. Bullard4Eric A. Weaver5David Steffen6Sathish Kumar Natarajan7Thomas M. Petro8Asit K. Pattnaik9School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USASchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USASchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Oral Biology, University of Nebraska Medical Center, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USASchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USASchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USAZika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate.https://www.mdpi.com/2076-393X/7/3/112Zika virusNS1 proteinglycosylationattenuationvaccine candidate |
| spellingShingle | Arun S. Annamalai Aryamav Pattnaik Bikash R. Sahoo Zack P. Guinn Brianna L. Bullard Eric A. Weaver David Steffen Sathish Kumar Natarajan Thomas M. Petro Asit K. Pattnaik An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model Vaccines Zika virus NS1 protein glycosylation attenuation vaccine candidate |
| title | An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model |
| title_full | An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model |
| title_fullStr | An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model |
| title_full_unstemmed | An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model |
| title_short | An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model |
| title_sort | attenuated zika virus encoding non glycosylated envelope e and non structural protein 1 ns1 confers complete protection against lethal challenge in a mouse model |
| topic | Zika virus NS1 protein glycosylation attenuation vaccine candidate |
| url | https://www.mdpi.com/2076-393X/7/3/112 |
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