Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines
Abstract
:1. Introduction
2. VLP-Based Flavivirus Vaccines
2.1. VLP-Based Vaccines against ZIKV Infection
2.2. VLP-Based Vaccines against DENV Infection
2.2.1. VLP-Based DENV Vaccines
2.2.2. Chimeric DENV VLP-Based Vaccines
2.2.3. Factors Affecting the Production or Packaging of DENV VLPs
2.3. VLP-Based Vaccines against WNV Infection
2.3.1. VLP-Based WNV Vaccines
2.3.2. Chimeric WNV VLP-Based Vaccine
2.3.3. Factors Affecting the Production or Packaging of WNV VLPs
2.4. VLP-Based Vaccines against JEV Infection
2.4.1. VLP-Based JEV Vaccines
2.4.2. Chimeric or Vectored JEV VLPs
2.4.3. Factors Affecting JEV VLP Production
3. Prospects and Challenge of VLP-Based Flavivirus Vaccines
4. Other Potential Applications of Flavivirus VLPs
4.1. Diagnostic Assays of VLPs for Flavivirus Detection
4.2. Flavivirus VLPs Can Be Used as Tools for Antiviral Drug Screening
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Expression System | VLP Components | Animal Model | Virus Strain | Immune Response | Clinical Trials | Ref. |
---|---|---|---|---|---|---|
Baculovirus-insect cells | prM-E | BALB/c mice | SZ-WIV01 | Stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses | No | [40] |
HEK293 cells | prM-E | CB6F1 and AG129 mice | African MR766 and Brazilian SPH2015 | Induced high ZIKV-specific neutralizing antibody titers and protected mice against weight loss, morbidity and mortality | No | [59] |
HEK293 cells | prM-E | Interferon deficient AG129 mice and BALB/c mice | H/PF/2013 | Induced neutralizing antibodies | No | [60] |
293T cells | C-prM-E and prM-E | BALB/c mice | PRVABC59 | Both prM-E- and C-prM-E-based VLP vaccines were highly effective in generating neutralizing antibodies, with the latter being more potent | No | [63] |
Nicotiana benthamiana plants | E protein domain III (zDIII) | C57BL/6 mice | PRVABC59 | Evoked potent neutralizing antibody and cellular immune responses; Circumvented induction of antibodies with ADE activity for DENV infection | No | [65] |
Yeast Pichia pastoris | DIII | BALB/c mice and AG129 mice | SPH2015 | Induced ZIKV-specific neutralizing antibodies, with no discernible ADE capacity | No | [64] |
Expression System | VLP Components | Animal Model | Virus Strain | Immune Response | Clinical Trials | Ref. |
---|---|---|---|---|---|---|
Yeast Pichia pastoris | C-prM-E | rabbits | Singapore strain S275/90 | Induced neutralizing antibodies | No | [67] |
Expi293TM cells | C-prM-E | BALB/c mice | DENV-2 Th-36 | Mice immunized with the VLP vaccine produced at 31 °C elicited the highest titer of neutralizing antibodies when compared to those elicited by equivalent doses of the vaccine produced at 37 °C | No | [68] |
Baculovirus-insect cells | prM-E | BALB/c mice | SZ-WIV01 | Stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers, and potent memory T cell responses | No | [40] |
Yeast Pichia pastoris | prM-E | BALB/c mice | DENV-1 GZ01/95 | Induced neutralizing antibodies and T cell responses | No | [69] |
293T cells | prM-E | BALB/c mice | DENV1 GZ01/95, DENV2 ZS01/01, DENV3 H87, DENV4 H241 | Induced VLP-specific IgG and neutralizing antibodies, as well as cellular immune responses | No | [71] |
HEK293 cells | prM-E | No test | DENV1 WestPac-74, DENV2 S16803, DENV3 CH53489, DENV4 TVP-376 | No test | No | [48] |
Mosquito cells | prM-E | BALB/c mice and cynomolgus macaques | DENV2 03-0420 and NS1-123 | With the help of adjuvants, the VLPs induced strong virus neutralizing antibodies. | No | [73] |
Yeast Pichia pastoris | prM-E | BALB/c mice | DENV1 GZ01/95, DENV2 ZS01/01, DENV3 H87, DENV4 H241 | The tetravalent VLPs induced humoral and cellular immune responses against all four dengue virus serotypes. The antibody levels were higher with tetravalent than with monovalent immunization | No | [52] |
FreeStyle 293F cells | prM-E with an F108 mutation in the fusion loop of E | BALB/c mice | DENV1, Western Pacific strain, DENV2, S1 vaccine strain, DENV3, Singapore 8120/95 strain, DENV4, ThD4_0476_97 strain | The tetravalent vaccine elicited potent neutralizing antibody responses against all four DENV serotypes, with ADE not observed against any serotype at a 1:10 serum dilution | No | [50] |
Yeast Pichia pastoris | E | BALB/c and AG129 mice | DENV2 New Guinea | Induced potent DENV-2-specific neutralizing antibodies and protected AG129 mice against lethal challenge with a virulent DENV-2 strain | No | [72] |
Yeast Pichia pastoris | E | BALB/c mice | DENV1 WP74, DENV4 TVP-360, DENV3 CH-53489 | Elicited EDIII-specific neutralizing antibody response in mice | No | [70,78,81] |
Yeast Pichia pastoris | EDIII | BALB/c mice | DENV2 (unmentioned strain) | Elicited DENV-2-specific antibodies which could neutralize its infectivity | No | [79] |
E. coli | EDIII | BALB/c mice | DENV2 (unmentioned strain) | Induced specific antibodies capable of binding and neutralizing the infectivity of DENV2 | No | [80] |
Yeast Pichia pastoris | E protein of DENV1 and DENV2 | BALB/c and AG129 mice | DENV1 WP74 and DENV2 New Guinea | The bivalent mosaic VLPs preserved the serotype-specific antigenic integrity of its two component proteins and elicited EDIII-specific neutralizing antibodies which lacked discernible ADE potential | No | [82] |
Yeast Pichia pastoris | E protein of DENV1, DENV2, DENV3, DENV4 | BALB/c and AG129 mice | DENV1 West Pac-74, DENV2 S16803, DENV3 CH53489, DENV4 TVP-360 | The tetravalent VLPs were highly immunogenic and elicited EDIII-specific neutralizing antibodies against all four DENV serotypes, and they did not promote ADE in vivo | No | [83] |
Yeast Pichia pastoris | EDIII of DENV1, DENV2, DENV3, DENV4 | BALB/c, AG129, C57BL-6, C3H and Macaques | DENV1 West Pac-74, DENV2 PR159-S1/69, DENV3 H87/56, DENV4 H241-P | The tetravalent VLPs elicited serotype-specific neutralizing antibodies effective against all four DENV serotypes with negligible ADE potential | No | [86] |
Expression System | VLP Components | Animal Model | Virus Strain | Immune Response | Clinical Trials | Ref. |
---|---|---|---|---|---|---|
E. Coli BL21DE3 | DIII | BALB/c mice | WNV NY99 | Three injections of the vaccine induced high titers of virus-neutralizing antibodies and completely protected mice from WNV infection | No | [94] |
Baculovirus-insect cells | DIII | BALB/c mice | WNV Kunjin | Although relatively modest, DENV- and WNV-specific neutralizing antibodies were induced | No | [93] |
E. coli | DIII | BALB/c mice | F101 New York | The VLP vaccine induced a broad spectrum of DIII-specific IgM, IgG1 and IgG2a/b antibodies | No | [95] |
Herpes simplex virus-1 d106 recombinant virus-Vero cells | prM-E | BALB/c mice | unknown | The VLP vaccine induced a specific anti-WNV IgG antibody response in immunized mice | No | [55] |
Baculovirus-insect cells | C, M and E | Not used | NY99034 EDV | Not tested | No | [96] |
Expression System | VLP Components | Animal Model | Virus Strain | Immune Response | Clinical Trials | Ref. |
---|---|---|---|---|---|---|
J12#26 stable cell line | E | BALB/c mice | Beijing-1 | Induced specific humoral and cell-mediated responses which were enhanced by the addition of adjuvants | No | [109] |
Silkworm pupae | E | Mice and rabbits | Muar | Immunized mice and rabbit antisera showed plaque inhibition potency against homologous Muar and heterologous Nakayama, but less potency to Beijing-1 strain. Mixed immune rabbit antisera led to an increase in the antibody reaction to Beijing-1 strain | No | [111] |
Silkworm Bm-N cells | prM-E | Mice and rabbits | Nakayma | Induced virus-neutralizing antibodies against Nakayama, Beijing-1, and Muar strains | No | [110] |
CHO-heparan sulfate-deficient cell derived stable cell line | prM-E | Mice and swine | GI YL2009-4, GI TC2009-1, GIII SA14-14-2, GIII T1P1, GIII CH1392, GIII CJN, CII JKT1749, GIV JKT7003 | GI-VLP-immunized mice and swine produced cross-protected antibody against GI and GIII JEVs | No | [112] |
BJ-ME BHK21 stable cell line | prM-E | BALB/c mice | SA14-14-2 | Elicited high titers of neutralizing antibodies which conferred 100% protection against lethal JEV challenge | No | [104] |
Baculovirus-insect cells | prM-E | BALB/c mice | JEV-P3 | Performed complete protection against viral challenge and significantly relieved pathological changes in mouse brain | No | [107] |
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Zhang, N.; Li, C.; Jiang, S.; Du, L. Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines. Vaccines 2020, 8, 481. https://doi.org/10.3390/vaccines8030481
Zhang N, Li C, Jiang S, Du L. Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines. Vaccines. 2020; 8(3):481. https://doi.org/10.3390/vaccines8030481
Chicago/Turabian StyleZhang, Naru, Chaoqun Li, Shibo Jiang, and Lanying Du. 2020. "Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines" Vaccines 8, no. 3: 481. https://doi.org/10.3390/vaccines8030481
APA StyleZhang, N., Li, C., Jiang, S., & Du, L. (2020). Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines. Vaccines, 8(3), 481. https://doi.org/10.3390/vaccines8030481