A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge
The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV inf...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/4/821 |
| _version_ | 1797603322536919040 |
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| author | Aryamav Pattnaik Bikash R. Sahoo Lucas R. Struble Gloria E. O. Borgstahl You Zhou Rodrigo Franco Raul G. Barletta Fernando A. Osorio Thomas M. Petro Asit K. Pattnaik |
| author_facet | Aryamav Pattnaik Bikash R. Sahoo Lucas R. Struble Gloria E. O. Borgstahl You Zhou Rodrigo Franco Raul G. Barletta Fernando A. Osorio Thomas M. Petro Asit K. Pattnaik |
| author_sort | Aryamav Pattnaik |
| collection | DOAJ |
| description | The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV. |
| first_indexed | 2024-03-11T04:27:34Z |
| format | Article |
| id | doaj.art-e3cb7424d3e346c6b8be648771444311 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T04:27:34Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-e3cb7424d3e346c6b8be6487714443112023-11-17T21:42:13ZengMDPI AGVaccines2076-393X2023-04-0111482110.3390/vaccines11040821A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus ChallengeAryamav Pattnaik0Bikash R. Sahoo1Lucas R. Struble2Gloria E. O. Borgstahl3You Zhou4Rodrigo Franco5Raul G. Barletta6Fernando A. Osorio7Thomas 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, USAThe Eppley Institute for Cancer and Allied Diseases, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAThe Eppley Institute for Cancer and Allied Diseases, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, 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, 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, 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, USAThe severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.https://www.mdpi.com/2076-393X/11/4/821Zika virusenvelope protein domain IIIferritinnanoparticlesneutralizing antibody responsecell-mediated response |
| spellingShingle | Aryamav Pattnaik Bikash R. Sahoo Lucas R. Struble Gloria E. O. Borgstahl You Zhou Rodrigo Franco Raul G. Barletta Fernando A. Osorio Thomas M. Petro Asit K. Pattnaik A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge Vaccines Zika virus envelope protein domain III ferritin nanoparticles neutralizing antibody response cell-mediated response |
| title | A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge |
| title_full | A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge |
| title_fullStr | A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge |
| title_full_unstemmed | A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge |
| title_short | A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge |
| title_sort | ferritin nanoparticle based zika virus vaccine candidate induces robust humoral and cellular immune responses and protects mice from lethal virus challenge |
| topic | Zika virus envelope protein domain III ferritin nanoparticles neutralizing antibody response cell-mediated response |
| url | https://www.mdpi.com/2076-393X/11/4/821 |
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