Co-Immunization With CHIKV VLP and DNA Vaccines Induces a Promising Humoral Response in Mice

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.

[1]  J. Matthijnssens,et al.  A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate , 2020, Nature.

[2]  E. Rowan,et al.  Recent advances in therapeutic applications of neutralizing antibodies for virus infections: an overview , 2020, Immunologic Research.

[3]  Qingyuan Du,et al.  Candidate , 2012, Juan Perón.

[4]  L. Delang,et al.  Antiviral drug discovery against arthritogenic alphaviruses: tools and molecular targets. , 2019, Biochemical pharmacology.

[5]  Leiliang Zhang,et al.  Recent Progress in Vaccine Development Against Chikungunya Virus , 2019, Front. Microbiol..

[6]  Haoran Peng,et al.  Construction and identification of chikungunya virus infectious clones , 2019 .

[7]  Bo Zhang,et al.  Infectious Chikungunya Virus (CHIKV) with a Complete Capsid Deletion: a New Approach for a CHIKV Vaccine , 2019, Journal of Virology.

[8]  Yang Yang,et al.  Humoral and cellular immunity against both ZIKV and poxvirus is elicited by a two-dose regimen using DNA and non-replicating vaccinia virus-based vaccine candidates. , 2019, Vaccine.

[9]  A. Reyes-Sandoval,et al.  51 years in of Chikungunya clinical vaccine development: A historical perspective , 2019, Human vaccines & immunotherapeutics.

[10]  T. Ross,et al.  Vaccination with a chikungunya virus-like particle vaccine exacerbates disease in aged mice , 2019, PLoS neglected tropical diseases.

[11]  E. Reisinger,et al.  Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial , 2018, The Lancet.

[12]  Ali Zaid,et al.  Attenuation and Stability of CHIKV-NoLS, a Live-Attenuated Chikungunya Virus Vaccine Candidate , 2018, Vaccines.

[13]  Leiliang Zhang,et al.  Fatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1 , 2018, Journal of Virology.

[14]  D. Kovanich,et al.  Ubiquitin‐Conjugating Enzyme E2 L3 is Downregulated by the Chikungunya Virus nsP2 Protease , 2018, Proteomics. Clinical applications.

[15]  L. Rénia,et al.  Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity , 2018, Scientific Reports.

[16]  A. Powers.  Vaccine and Therapeutic Options To Control Chikungunya Virus , 2017, Clinical Microbiology Reviews.

[17]  Myoung-Heon Lee,et al.  Coinjection of a vaccine and anti‐viral agents can provide fast‐acting protection from foot‐and‐mouth disease , 2017, Antiviral research.

[18]  S. Weaver,et al.  Development of Vaccines for Chikungunya Fever. , 2016, The Journal of infectious diseases.

[19]  A. Saha,et al.  Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate , 2016, PLoS neglected tropical diseases.

[20]  N. Sardesai,et al.  Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus , 2016, The Journal of infectious diseases.

[21]  J. Chu,et al.  Chikungunya Virus , 2016, Methods in Molecular Biology.

[22]  N. Wlodarchak,et al.  Dissecting the Role of E2 Protein Domains in Alphavirus Pathogenicity , 2015, Journal of Virology.

[23]  Yun-zhou Yu,et al.  Co-immunization with DNA and protein mixture: A safe and efficacious immunotherapeutic strategy for Alzheimer's disease in PDAPP mice , 2015, Scientific Reports.

[24]  J. Mascola,et al.  Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial , 2014, The Lancet.

[25]  Jian-Dong Li,et al.  Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis. , 2014, Antiviral research.

[26]  L. Ng,et al.  Prime-Boost Immunization Strategies against Chikungunya Virus , 2014, Journal of Virology.

[27]  C. Sorzano,et al.  A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection , 2014, Journal of Virology.

[28]  J. Vlak,et al.  Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein E1 or E2 subunits. , 2013, Vaccine.

[29]  S. Reed,et al.  HIV/SIV DNA vaccine combined with protein in a co-immunization protocol elicits highest humoral responses to envelope in mice and macaques. , 2013, Vaccine.

[30]  K. Kim,et al.  Reovirus Cell Entry Requires Functional Microtubules , 2013, mBio.

[31]  M. Kielian,et al.  Cross-Inhibition of Chikungunya Virus Fusion and Infection by Alphavirus E1 Domain III Proteins , 2013, Journal of Virology.

[32]  Just M. Vlak,et al.  Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells , 2013, PLoS neglected tropical diseases.

[33]  N. Sardesai,et al.  Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine. , 2013, Viral immunology.

[34]  Yuzhang Wu,et al.  Caveolin-1–Mediated Negative Signaling Plays a Critical Role in the Induction of Regulatory Dendritic Cells by DNA and Protein Coimmunization , 2012, The Journal of Immunology.

[35]  N. Sardesai,et al.  A DNA Vaccine against Chikungunya Virus Is Protective in Mice and Induces Neutralizing Antibodies in Mice and Nonhuman Primates , 2011, PLoS neglected tropical diseases.

[36]  M. Rossmann,et al.  Structural Changes of Envelope Proteins During Alphavirus Fusion , 2010, Nature.

[37]  Thibaut Larcher,et al.  Chikungunya Virus Arthritis in Adult Wild-Type Mice , 2010, Journal of Virology.

[38]  Nicolas Gangneux,et al.  Prophylaxis and Therapy for Chikungunya Virus Infection , 2009, The Journal of infectious diseases.

[39]  N. Sardesai,et al.  Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus. , 2008, Vaccine.

[40]  Scott C Weaver,et al.  Chimeric alphavirus vaccine candidates for chikungunya. , 2008, Vaccine.

[41]  Min Ding,et al.  SSB peptide and DNA co-immunization induces inhibition of anti-dsDNA antibody production in rabbits. , 2008, Chinese medical journal.

[42]  Jinyao Li,et al.  Enhanced contraceptive response by co‐immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary , 2007, The journal of gene medicine.

[43]  T. Ishikawa,et al.  Co-immunization with West Nile DNA and inactivated vaccines provides synergistic increases in their immunogenicities in mice. , 2007, Microbes and infection.

[44]  J. Mascola,et al.  A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates , 2005, Journal of Virology.

[45]  Pamela G. Guren,et al.  Candidates , 1982, Otolaryngology–Head and Neck Surgery.