Self-Assembling Nanovaccine Confers Complete Protection Against Zika Virus Without Causing Antibody-Dependent Enhancement

The Zika virus (ZIKV) epidemic poses a substantial threat to the public, and the development of safe and effective vaccines is a demanding challenge. In this study, we constructed a kind of self-assembling nanovaccine which confers complete protection against ZIKV infection. The ZIKV envelop protein domain III (zEDIII) was presented on recombinant human heavy chain ferritin (rHF) to form the zEDIII-rHF nanoparticle. Immunization of mice with zEDIII-rHF nanoparticle in the absence of an adjuvant induced robust humoral and cellular immune responses. zEDIII-rHF vaccination conferred complete protection against lethal infection with ZIKV and eliminated pathological symptoms in the brain. Importantly, the zEDIII-rHF nanovaccine induced immune response did not cross-react with dengue virus-2, overcoming the antibody-dependent enhancement (ADE) problem that is a safety concern for ZIKV vaccine development. Our constructed zEDIII-rHF nanovaccine, with superior protective performance and avoidance of ADE, provides an effective and safe vaccine candidate against ZIKV.

[1]  S. Ubol,et al.  Peritoneal Administration of a Subunit Vaccine Encapsulated in a Nanodelivery System Not Only Augments Systemic Responses against SARS-CoV-2 but Also Stimulates Responses in the Respiratory Tract , 2021, Viruses.

[2]  Zheng Jin,et al.  Intranasal immunization with O-2′-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens , 2021, Journal of Nanobiotechnology.

[3]  R. Folkerth,et al.  A fatal case report of antibody-dependent enhancement of dengue virus type 1 following remote Zika virus infection , 2021, BMC Infectious Diseases.

[4]  G. Gao,et al.  Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch , 2021, Nature Immunology.

[5]  Justin M. Richner,et al.  A Dengue Virus Serotype 1 mRNA-LNP Vaccine Elicits Protective Immune Responses , 2021, Journal of Virology.

[6]  Tao Hu,et al.  Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study. , 2021, Bioconjugate chemistry.

[7]  W. Chiu,et al.  A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice , 2021, ACS central science.

[8]  J. Saiz,et al.  The combined vaccination protocol of DNA/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses , 2021, Emerging microbes & infections.

[9]  Azizul Haque,et al.  Efforts at COVID-19 Vaccine Development: Challenges and Successes , 2020, Vaccines.

[10]  P. Karmali,et al.  CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine , 2020, Science Advances.

[11]  K. Ono,et al.  An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency , 2020, Scientific Reports.

[12]  J. Ravetch,et al.  The role of IgG Fc receptors in antibody-dependent enhancement , 2020, Nature Reviews Immunology.

[13]  Young Chan Kim,et al.  Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines , 2020, Vaccines.

[14]  L. Ferreira,et al.  CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection , 2020, Cell reports.

[15]  F. Krammer,et al.  Zika virus envelope nanoparticle antibodies protect mice without risk of disease enhancement , 2020, EBioMedicine.

[16]  M. Diamond,et al.  A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection , 2019, Nature Immunology.

[17]  M. Koopmans,et al.  The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis , 2019, PLoS pathogens.

[18]  Sandra Jesus,et al.  Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant , 2019, Pharmaceutics.

[19]  J. Saiz,et al.  A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice , 2018, Scientific Reports.

[20]  H. Schuitemaker,et al.  Adenoviral vector type 26 encoding Zika virus (ZIKV) M-Env antigen induces humoral and cellular immune responses and protects mice and nonhuman primates against ZIKV challenge , 2018, PloS one.

[21]  A. Iwasaki,et al.  Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection , 2018, Nature Communications.

[22]  A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein , 2018, Nature Communications.

[23]  Y. Zhang,et al.  Zika Virus Attenuation by Codon Pair Deoptimization Induces Sterilizing Immunity in Mouse Models , 2018, Journal of Virology.

[24]  Stephen J. Thomas,et al.  Zika vaccines and therapeutics: landscape analysis and challenges ahead , 2018, BMC Medicine.

[25]  S. Cassadou,et al.  Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas , 2018, The New England journal of medicine.

[26]  Jianjun Chen,et al.  Intranasal Nanovaccine Confers Homo- and Hetero-Subtypic Influenza Protection. , 2018, Small.

[27]  J. Tregoning,et al.  Adjuvanted influenza vaccines , 2018, Human vaccines & immunotherapeutics.

[28]  J. Mascola,et al.  Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials , 2017, The Lancet.

[29]  H. Bossin,et al.  Zika virus in French Polynesia 2013-14: anatomy of a completed outbreak. , 2017, The Lancet. Infectious diseases.

[30]  Suh-Chin Wu,et al.  Zika virus structural biology and progress in vaccine development. , 2017, Biotechnology advances.

[31]  G. Gao,et al.  Structures of Zika Virus E & NS1: Relations with Virus Infection and Host Immune Responses. , 2018, Advances in experimental medicine and biology.

[32]  D. Fremont,et al.  Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization and protection against divergent Zika viruses , 2018, Emerging Microbes & Infections.

[33]  WenJinsheng,et al.  T Cell Immunity to Zika and Dengue Viral Infections , 2017 .

[34]  G. Gao,et al.  CD8+ T Cell Immune Response in Immunocompetent Mice during Zika Virus Infection , 2017, Journal of Virology.

[35]  Ming Yang,et al.  Immunization of Zika virus envelope protein domain III induces specific and neutralizing immune responses against Zika virus. , 2017, Vaccine.

[36]  Michael E. Woolley,et al.  Zika virus: History, epidemiology, transmission, and clinical presentation , 2017, Journal of Neuroimmunology.

[37]  K. Sumathy,et al.  Protective efficacy of Zika vaccine in AG129 mouse model , 2017, Scientific Reports.

[38]  A. Barrett,et al.  A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models , 2017, Nature Medicine.

[39]  Justin M. Richner,et al.  Modified mRNA Vaccines Protect against Zika Virus Infection , 2017, Cell.

[40]  K. Stiasny,et al.  The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis , 2017, Microbiology and Molecular Biology Reviews.

[41]  Mingyue Xu,et al.  Detection of Zika virus by SYBR green one-step real-time RT-PCR. , 2016, Journal of virological methods.

[42]  Jessica Jimenez,et al.  Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys , 2016, Science.

[43]  M. Beltramello,et al.  Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection , 2016, Science.

[44]  D. Burton,et al.  Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles , 2016, Nature Communications.

[45]  S. Kashima,et al.  Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic , 2016, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[46]  Gengfu Xiao,et al.  Isolation and characterization of Zika virus imported to China using C6/36 mosquito cells , 2016, Virologica Sinica.

[47]  J. Chu,et al.  Development and Evaluation of a SYBR Green–Based Real-Time Multiplex RT-PCR Assay for Simultaneous Detection and Serotyping of Dengue and Chikungunya Viruses , 2015, The Journal of Molecular Diagnostics.

[48]  John P. Moore,et al.  Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity , 2015, Retrovirology.

[49]  Lu Lu,et al.  Advancements in the development of subunit influenza vaccines. , 2015, Microbes and infection.

[50]  B. Bhushan,et al.  Ferritin nanocages: a novel platform for biomedical applications. , 2014, Journal of biomedical nanotechnology.

[51]  J. Whittle,et al.  Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies , 2013, Nature.

[52]  Gregory A. Poland,et al.  Nanovaccinology: the next generation of vaccines meets 21st century materials science and engineering. , 2012, Vaccine.

[53]  A. Bærug,et al.  Challenges and Successes , 2012, Journal of human lactation : official journal of International Lactation Consultant Association.

[54]  K. Schwarz,et al.  Efficient induction of mucosal and systemic immune responses by virus‐like particles administered intranasally: implications for vaccine design , 2008, European journal of immunology.

[55]  S. Kalayanarooj,et al.  Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. , 2007, The Journal of general virology.

[56]  K. Yoon,et al.  Antibody-dependent enhancement of virus infection and disease. , 2003, Viral immunology.

[57]  M Aguet,et al.  Functional role of type I and type II interferons in antiviral defense. , 1994, Science.