A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge

Authors

Aryamav Pattnaik, University of Nebraska-Lincoln
Bikash R. Sahoo, University of Nebraska-LincolnFollow
Lucas R. Struble, University of Nebraska Medical CenterFollow
Gloria E. O. Borgstahl, University of Nebraska Medical CenterFollow
You Zhou, University of Nebraska - LincolnFollow
Rodrigo Franco, University of Nebraska - LincolnFollow
Raul G. Barletta, University of Nebraska - LincolnFollow
Fernando A. Osorio, University of Nebraska - LincolnFollow
Thomas M. Petro, University of Nebraska Medical CenterFollow
Asit K. Pattnaik, University of Nebraska - LincolnFollow

Date of this Version

4-10-2023

Citation

Pattnaik, A.; Sahoo, B.R.; Struble, L.R.; Borgstahl, G.E.O.; Zhou, Y.; Franco, R.; Barletta, R.G.; Osorio, F.A.; Petro, T.M.; Pattnaik, A.K. A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge. Vaccines 2023, 11, 821. https://doi.org/10.3390/ vaccines11040821

Comments

Open access.

Abstract

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.