Review
Immunology
Jue Hou, Weijian Ye, Jianzhu Chen
Summary: Dengue is a common mosquito-borne disease caused by four closely related viruses. Developing a vaccine that can protect against all four virus strains without adverse effects is a challenge. Several tetravalent live attenuated vaccine candidates have entered clinical trials.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Materials Science, Biomaterials
Rafiq Ahmad Khan, Farhan Ahmed, Sumbul Afroz, Nooruddin Khan
Summary: This study introduced a new strategy of encapsulating the EDIII domain of all serotypes of DENV into PLGA nanoparticles, and the tetravalent nano formulation combined with TLR agonists showed enhanced immunological efficacy, triggering robust antibody responses and improved production of serotype-specific neutralizing antibodies.
BIOMATERIALS SCIENCE
(2022)
Article
Immunology
Isamu Tsuji, David Dominguez, Michael A. Egan, Hansi J. Dean
Summary: A novel avidity assay using biolayer interferometry and dengue virus-like particles was developed to assess antibody affinity maturation. Vaccination with tetravalent dengue vaccine candidate (TAK-003) increased avidity index, which remained high throughout 1 year postvaccination.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Ramil R. Mintaev, Dina V. Glazkova, Olga V. Orlova, Georgiy M. Ignatyev, Alexey S. Oksanich, German A. Shipulin, Elena V. Bogoslovskaya
Summary: Dengue fever is a global health problem, affecting over 100 million people annually. Vaccination is the most effective prevention strategy, but the development of vaccines is hindered by the risk of antibody-dependent enhancement. This article presents the development of an MVA-d34 vaccine against dengue virus, using safe and effective MVA viral vector. The vaccine targets the DIII domains of the envelope protein, which do not cause enhanced infection. Immunized mice generate a humoral response against all four dengue virus serotypes, and their sera have virus-neutralizing activity against dengue serotype 2. The MVA-d34 vaccine shows promise as a candidate vaccine against dengue fever.
Article
Immunology
Daniela Michlmayr, Paulina Andrade, Eduardo J. M. Nascimento, Allan Parker, Parnal Narvekar, Hansi J. Dean, Eva Harris
Summary: This study analyzed the specific and cross-reactive memory B cell responses to dengue virus in individuals who received a tetravalent vaccine candidate. The results showed that tetravalent vaccination induced type-specific memory B cells, demonstrating a significant contribution from all 4 components of the vaccine to the DENV-specific memory B cell response.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Amina Basheer, Syed Babar Jamal, Badr Alzahrani, Muhammad Faheem
Summary: Dengue fever is a mosquito-borne disease that affects approximately 3.9 billion people globally each year. Currently, there is no available vaccine or drug for dengue virus infection. In this study, researchers designed a tetravalent subunit multi-epitope vaccine targeting different proteins from each serotype. The vaccine has shown potential to elicit a strong immune response against all dengue serotypes without causing any adverse effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Kum-Kang So, Jeesun Chun, Nguyen Ngoc Luong, Hee-Won Seo, Dae-Hyuk Kim
Summary: The study demonstrated the efficient production of various immunocomplex structures of the target protein in Saccharomyces cerevisiae for future development of oral and injectable vaccines against pathogens.
BIOTECHNOLOGY LETTERS
(2021)
Article
Immunology
Li Qi, Yanqing Sun, Michal Juraska, Zoe Moodie, Craig A. Magaret, Fei Heng, Lindsay N. Carpp, Peter B. Gilbert
Summary: In the CYD14 trial, high neutralizing antibody (nAb) titers to the vaccine-insert dengue strains were associated with lower risk of symptomatic, virologically-confirmed dengue (VCD). The efficacy of the vaccine against VCD was higher when the dengue prM/E amino acid sequences were closer to the vaccine inserts.
Article
Immunology
Peifang Sun, Vihasi Jani, Alison Johnson, Ying Cheng, Nishith Nagabhushana, Maya Williams, Brian J. Morrison, Gabriel Defang
Summary: TLAV vaccination enhances innate immune gene expression, provides better protection against dengue virus, and more effectively boosts T cell IFN gamma response compared to TDNA and TPIV vaccines. TPIV vaccination alone induces higher B-Mem and weaker IFN gamma response, but significantly enhances T cell response when boosted with TLAV vaccination.
Article
Immunology
Kirill Nemirov, Pierre Authie, Philippe Souque, Fanny Moncoq, Amandine Noirat, Catherine Blanc, Maryline Bourgine, Laleh Majlessi, Pierre Charneau
Summary: Dengue virus (DENV) is a major cause of dengue fever, including severe forms such as hemorrhagic dengue and dengue shock syndrome. Despite intensive vaccine research, a universally accepted vaccine against dengue fever has not been developed yet. This study developed a tetravalent T-cell vaccine candidate against DENV, which showed significant protective effects against all four DENV serotypes in a preclinical infection model.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Guntur Fibriansah, Elisa X. Y. Lim, Jan K. Marzinek, Thiam-Seng Ng, Joanne L. Tan, Roland G. Huber, Xin-Ni Lim, Valerie S. Y. Chew, Victor A. Kostyuchenko, Jian Shi, Ganesh S. Anand, Peter J. Bond, James E. Crowe, Shee-Mei Lok
Summary: Dengue virus has four serotypes (DENV1-4) with different strains within each serotype. The virus can exhibit smooth or bumpy surface morphologies at 37 degrees C, depending on the strain. High-affinity therapeutic antibodies are able to neutralize diverse morphologies of dengue virus.
Article
Immunology
Hong-Jyun Huang, Martyr Yang, Hsin-Wei Chen, Shuying Wang, Chih-Peng Chang, Tzong-Shiann Ho, Yu-San Kao, Sen-Mao Tien, Hsing-Han Lin, Po-Chun Chang, Yen-Chung Lai, Yu-Peng Hsiao, Yi-Ling Liu, Chiao-Hsuan Chao, Robert Anderson, Trai-Ming Yeh, Yee-Shin Lin, Shu-Wen Wan
Summary: This study developed a modified DENV vaccine candidate with enhanced features by combining modifications of two DENV proteins. The vaccine candidate showed protective effects against DENV infection in a mouse model, indicating its potential clinical application.
Article
Immunology
Inge LeFevre, Lulu Bravo, Nicolas Folschweiller, Eduardo Lopez Medina, Edson Duarte Moreira, Francesco Nordio, Mayuri Sharma, Leslie M. Tharenos, Vianney Tricou, Veerachai Watanaveeradej, Peter J. Winkle, Shibadas Biswal
Summary: Immunobridging is an important methodology used to estimate vaccine efficacy in populations not included in clinical studies, and has been successfully applied in vaccine development. Dengue, a mosquito-borne viral disease, was traditionally considered a pediatric disease but is now a global threat to people of all ages. This study bridged immunogenicity data from a phase 3 efficacy study in children and adolescents with an immunogenicity study in adults, and found comparable immune responses following two doses of the TAK-003 vaccine, supporting its potential efficacy in adults.
Article
Immunology
Te-Sheng Lien, Der-Shan Sun, Shih-Che Hung, Wen-Sheng Wu, Hsin-Hou Chang
Summary: The study shows that the dengue virus envelope protein domain III can induce neutrophil NETosis processes, and inhibition of Nlrp3 inflammasome can suppress this process, providing a new molecular target for treating dengue-induced inflammatory pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Qier Chen, Rong Li, Bolin Wu, Xu Zhang, Hui Zhang, Ran Chen
Summary: Dengue fever, caused by the dengue virus, is a global health threat. Developing a safe and effective vaccine is challenging due to antibody-dependent enhancement (ADE). Researchers have successfully developed a tetravalent nanoparticle vaccine that induces potent immune responses and protects against DENV-2 and DENV-3 challenges in mice.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Jhe-Jhih Lin, Pei-Jung Chung, Shih-Syong Dai, Wan-Ting Tsai, Yu-Feng Lin, Yi-Ping Kuo, Kuen-Nan Tsai, Chia-Hao Chien, De-Jiun Tsai, Ming-Sian Wu, Pei-Yun Shu, Andrew Yueh, Hsin-Wei Chen, Chun-Hong Chen, Guann-Yi Yu
Summary: Dengue virus (DENV) is causing an increase in infections due to global urbanization and international travel. A study on the TW2015 virus, which caused outbreaks in Taiwan in 2015, found it to be highly virulent in interferon-deficient mice and have high transmissibility to Aedes mosquitoes. The structural genes prM and E were identified as key virulence determinants in host and vector transmissibility.
Article
Pharmacology & Pharmacy
Hui-Min Ho, Chiung-Yi Huang, Yu-Jhen Cheng, Kuan-Yin Shen, Tsai-Teng Tzeng, Shih-Jen Liu, Hsin-Wei Chen, Chung-Hsiung Huang, Ming-Hsi Huang
Summary: This study demonstrates that SQ@NP-adjuvanted vaccines can induce specific immune responses in mice and enhance vaccine efficacy. Furthermore, the use of SQ@NP as an adjuvant for the S-protein vaccine significantly enhances the secretion of cytokines in splenocytes, which is important for boosting immune responses.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Infectious Diseases
Kit Man Chai, Tsai-Teng Tzeng, Kuan-Yin Shen, Hung-Chun Liao, Jhe-Jhih Lin, Mei-Yu Chen, Guann-Yi Yu, Horng-Yunn Dou, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: Efficient vaccines against COVID-19 are urgently needed, with the spike protein of SARS-CoV-2 as a major target. A DNA vaccine delivery via electroporation showed promising results in inducing antibodies and neutralizing antibodies, especially with the ability to induce strong Th1-biased responses.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Hung-Chun Liao, Wan-Ling Wu, Chen-Yi Chiang, Min-Syuan Huang, Kuan-Yin Shen, Yu-Ling Huang, Suh-Chin Wu, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: During the COVID-19 pandemic, global mass vaccination is crucial for achieving herd immunity. The study shows that the S-Trimer vaccine, when adjuvanted with SWE, induces strong antibody and cellular immune responses, providing neutralizing antibodies against the original and variant strains of SARS-CoV-2. Additionally, the SWE adjuvant allows for a lower vaccine dosage while maintaining effectiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Hong-Jyun Huang, Martyr Yang, Hsin-Wei Chen, Shuying Wang, Chih-Peng Chang, Tzong-Shiann Ho, Yu-San Kao, Sen-Mao Tien, Hsing-Han Lin, Po-Chun Chang, Yen-Chung Lai, Yu-Peng Hsiao, Yi-Ling Liu, Chiao-Hsuan Chao, Robert Anderson, Trai-Ming Yeh, Yee-Shin Lin, Shu-Wen Wan
Summary: This study developed a modified DENV vaccine candidate with enhanced features by combining modifications of two DENV proteins. The vaccine candidate showed protective effects against DENV infection in a mouse model, indicating its potential clinical application.
Article
Immunology
Jhe-Jhih Lin, Chih-Feng Tien, Yi-Ping Kuo, En-Ju Lin, Wei-Hsiang Tsai, Ming-Yu Chen, Pei-Ju Tsai, Yu-Wen Su, Nikhil Pathak, Jinn-Moon Yang, Chia-Yi Yu, Zih-Shiuan Chuang, Han-Chieh Wu, Wan-Ting Tsai, Shih-Syong Dai, Hung-Chun Liao, Kit Man Chai, Yu-Siang Su, Tsung-Hsien Chuang, Shih-Jen Liu, Hsin-Wei Chen, Horng-Yunn Dou, Feng-Jui Chen, Chiung-Tong Chen, Chin-Len Liao, Guann-Yi Yu
Summary: An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still needed. This study used a vesicular stomatitis virus (VSV)-based vector to express the SARS-CoV-2 Spike protein for better vaccine designs. The recombinant VSV-spike virus with C-terminal 19 amino acid truncation (S Delta 19 Rep) induced protective immunity against SARS-CoV-2 infection in hamsters. Mutations blocking enzymatic processing of the Spike protein were identified and found to enhance immune responses. Vaccination with the mutated virus provided high antibody response and protection against a lethal SARS-CoV-2 challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Tsai-Teng Tzeng, Kit Man Chai, Kuan-Yin Shen, Chia-Yi Yu, Shiu-Ju Yang, Wan-Chun Huang, Hung-Chun Liao, Fang-Feng Chiu, Horng-Yunn Dou, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: This study reports an electroacupuncture machine-based method for DNA vaccine delivery of the COVID-19 DNA vaccine. The method was found to efficiently induce neutralizing antibodies and Th1-biased immune responses in mice and provide protection against SARS-CoV-2 challenge in hamsters. T-cell epitope mapping revealed specific regions of reactivity. The method was deemed safe based on preclinical toxicology studies, and the raised antisera showed cross-neutralization against different variants of concern.
Article
Medicine, Research & Experimental
Wan-Ling Wu, Chen-Yi Chiang, Szu-Chia Lai, Chia-Yi Yu, Yu-Ling Huang, Hung-Chun Liao, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Summary: Most therapeutic monoclonal antibodies (mAbs) target the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, which is prone to mutations in variants. However, we identified mAbs that recognize the non-mutated S2 region of the spike protein and can neutralize SARS-CoV-2 infection and protect animals. Humanization of variable region sequences led to the selection of a high-affinity humanized mAb, hMab5.17, which effectively neutralized both SARS-CoV-2 and its variants. This suggests that an mAb targeting the S2 region could serve as a potential universal therapeutic for COVID-19.
Article
Multidisciplinary Sciences
Chih-Feng Tien, Wan-Ting Tsai, Chun Hwa Chen, Hui-Ju Chou, Mingzi M. Zhang, Jhe-Jhih Lin, En-Ju Lin, Shih-Syong Dai, Yueh-Hsin Ping, Chia-Yi Yu, Yi-Ping Kuo, Wei-Hsiang Tsai, Hsin-Wei Chen, Guann-Yi Yu
Summary: Post-translational modifications play critical roles in protein folding, stability, trafficking, and function. This study investigates the impact of glycosylation and palmitoylation on the maturation and infectivity of SARS-CoV-2 spike protein. The results show that mutations in specific motifs alter intracellular trafficking, glycosylation pattern, and infectivity of pseudoviruses, highlighting the importance of these modifications in the fusion and infection mediated by the S protein.
Article
Virology
Kuan-Yin Shen, Chung-Hsiang Yang, Chiung-Tong Chen, Hui-Min Ho, Fang-Feng Chiu, Chiung-Yi Huang, Hung-Chun Liao, Chia-Wei Hsu, Guann-Yi Yu, Ching-Len Liao, Hsin-Wei Chen, Ming-Hsi Huang, Shih-Jen Liu
Summary: The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. An Omicron-specific mRNA vaccine was designed to overcome this challenge. Animal studies showed that the vaccine generates non-neutralizing antibodies or cellular immunity that can recognize both Wuhan and Omicron variants, providing protection against Wuhan virus challenge.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Pharmacology & Pharmacy
Hui-Min Ho, Chiung-Yi Huang, Chung-Hsiang Yang, Shih-Jen Liu, Hsin-Wei Chen, Guann-Yi Yu, Jen-Kun Chen, Tsung-Hsien Chuang, Ming-Hsi Huang
Summary: Nasal spray vaccination is a promising strategy for inducing protection against respiratory SARS-CoV-2 coronavirus. This study demonstrates the potential of PELC:CpG as a mucosal adjuvant that enhances immune responses and cell-mediated immunity, which has implications for the development of a nasal spray vaccine against COVID-19.
Article
Immunology
Ming-Shu Hsieh, Mei-Yu Chen, Chia-Wei Hsu, Yu-Wen Tsai, Fang-Feng Chiu, Cheng-Lung Hsu, Chang-Ling Lin, Chiao-Chieh Wu, Ling-Ling Tu, Chen-Yi Chiang, Shih-Jen Liu, Ching-Len Liao, Hsin-Wei Chen
Summary: Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is a potential vaccine candidate produced by Staphylococcus aureus for reducing its virulence and biofilm formation. Recombinant lipidated FLIPr (rLF) was produced to increase its immunogenicity and showed to elicit potent anti-FLIPr responses and overcome FLIPr-mediated inhibition of phagocytosis. Additionally, rLF acts as an effective adjuvant by inducing strong and long-lasting immune responses in mice, supporting its potential use to enhance vaccine efficacy and abolish FLIPr-mediated immunosuppressive effects.
Article
Virology
Hung-Chun Liao, Min-Syuan Huang, Fang-Feng Chiu, Kit Man Chai, Ching-Len Liao, Suh-Chin Wu, Hsin-Wei Chen, Shih-Jen Liu
Summary: This study reports a novel COVID-19 vaccine that combines recombinant S protein with a DNA vaccine. The combination vaccine induces strong T-cell immune response and enhances immune indicators such as antibody titers. In animal experiments, hamsters vaccinated with the combination vaccine showed no weight loss and had low viral load in the lungs, indicating the important role of this vaccine in disease control.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Medicine, General & Internal
Hsing-Han Li, Matthew P. Su, Shih-Cheng Wu, Hsiao-Hui Tsou, Meng-Chun Chang, Yu-Chieh Cheng, Kuen-Nan Tsai, Hsin-Wei Wang, Guan-Hua Chen, Cheng-Kang Tang, Pei -Jung Chung, Wan-Ting Tsai, Li-Rung Huang, Yueh Andrew Yueh, Hsin-Wei Chen, Chao-Ying Pan, Omar S. Akbari, Hsiao-Han Chang, Guann-Yi Yu, John M. Marshall, Chun-Hong Chen
Summary: A study using a mouse model revealed the potential of mechanical transmission of dengue virus, independent of viral replication in mosquitoes. This finding suggests the possibility of larger outbreaks and has implications for vector control strategies. It also raises the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes.
Article
Cell Biology
Chen-Yi Chiang, Mei-Yu Chen, Chia-Wei Hsu, Chia-Yeh Liu, Yu-Wen Tsai, Hung-Chun Liao, Jia-Ying Yan, Zih-Shiuan Chuang, Hsin- Wang, Chien-Hsiung Pan, Chia-Yi Yu, Guann-Yi Yu, Ching-Len Liao, Shih-Jen Liu, Hsin-Wei Chen
Summary: This study generated high-quality monoclonal antibodies using a DNA prime-protein boost approach and found that one antibody displayed the best potency in terms of binding affinity and neutralizing capacity. This antibody was able to protect animals from SARS-CoV-2 infection. The results suggest that a combination of multiple monoclonal antibodies may be the best strategy for treating future SARS-CoV-2 variant outbreaks.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)