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

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.

Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine

“…We also measured the ζ-potential of Ferritin and FerritVac NPs, indicating negative values and within the range recently reported for a ferritin-based vaccine against the Zika virus by Rong et al. ( 42 ). Zeta potential measurements refer to the potential difference between the dispersion medium and the stationary layer of the fluid surrounding the dispersed particle, including the potential difference between the particle surface and surrounding liquid medium, representing the measure of colloidal stability of nanoparticles in dispersion ( 46 ).…”

“…Helicobacter pylori self-assembling ferritin has been used for the development of safe subunit nano vaccines, against some human and other mammalian viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV) ( 19 ), Influenza A virus ( 21 ), HIV ( 22 ), rotavirus A ( 23 ), SARS-CoV-2 ( 24 ), Canine distemper virus ( 25 ), classical swine fever virus ( 39 ), foot-and-mouth disease virus ( 40 ), hepatitis C virus ( 41 ), and Zika Virus ( 42 ), which have been produced in bacteria, insects and mammalian cells systems. In this study, we have for the first time used self-assembling ferritin nanocages as a vaccine platform against a non-mammalian viral pathogen (IHNV).…”

Nanoparticles and Antiviral Vaccines

“…Ferritin nanoparticles have been used to develop vaccines against ZIKV. Aryamav Pattnaik et al constructed a candidate vaccine with ferritin nanoparticles exhibiting Domain III (DIII) of ZIKV E protein [ 226 ]. Compared with immunogen monomers, the ferritin-based nanoparticles induced higher nAb responses and were capable of eliciting cell-mediated immune responses to eliminate virus-infected cells.…”

Vaccination against Epstein–Barr Latent Membrane Protein 1 Protects against an Epstein–Barr Virus-Associated B Cell Model of Lymphoma

“…Prior to vaccination, 20 µg per mouse of the TMV-peptide conjugate (delivering 2 µg of peptide) was diluted into 50 µL of phosphate-buffered saline (PBS), then combined with 50 µL of an AddaVax adjuvant (InvivoGen) for subcutaneous injection. AddaVax is a squalene-based oil-in-water adjuvant known to support both antibody production and cellular activation [33]. In total, 50 µg of the pc3.1 LMP1 plasmid was used for intramuscular vaccination for each mouse, and was diluted with 50% AddaVax (InvivoGen) adjuvant and administered in 25 µL to each quadriceps muscle.…”