Abstract
Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500000 reported cases of the severe forms of the disease-dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. Live attenuated D2 16681-PDK53 vaccine was first developed from Mahidol University, Thailand. This vaccine induced both humoral and cell-mediated immunity and lack of reactogeneticity in humans. Infectious cDNA clones of the virulent D2 16681 virus and its attenuated D2 16681-PDK53 were constructed. The attenuated virus elicited neutralizing antibodies in mice and monkeys and developed viremia in monkeys. At molecular level, patterns of cytokines which are immunological mediators released from human mononuclear cells obtained from dengue naive and immune donors infected with this attenuated virus compared with virulent virus were studied. In dengue naive PBMC, the virulent and attenuated clones induced alternation in expression of 25 and 24 versus 13 and 18 genes out of 268 genes on day 1 and 3. In dengue immune PBMC, the virulent and attenuated clones induced alternation in expression of 33 and 38 versus 25 and 29 genes on days 1 and 3. Up-regulation of IL-1β, IL-6, IL-8, IL-10, IFN-α, IFNγR, MIP-1α, MIP-1β, MIP-2α, VEGF and down-regulation of IL-4, IL-4R, IL-RII, MIF, RANTES, IGF-1, GM-CSF-2 were shown. This review pointed out the infectious clones of the attenuated D2 16681-PDK53 was safe and induced both neutralizing antibodies in vivo and cytokine gene expression in vitro at molecular level. Furthermore, the phenotypic markers of ideal dengue vaccine could be included the alteration of cytokine gene expression and cytokine production in human mononuclear cells.
Keywords: Dengue, vaccine, Humoral immunity, Cell-mediated immunity
Current Pharmaceutical Design
Title: Attenuated D2 16681-PDK53 Vaccine: Defining Humoral and Cell- Mediated Immunity
Volume: 15 Issue: 11
Author(s): J. Rabablert and S. Yoksan
Affiliation:
Keywords: Dengue, vaccine, Humoral immunity, Cell-mediated immunity
Abstract: Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500000 reported cases of the severe forms of the disease-dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. Live attenuated D2 16681-PDK53 vaccine was first developed from Mahidol University, Thailand. This vaccine induced both humoral and cell-mediated immunity and lack of reactogeneticity in humans. Infectious cDNA clones of the virulent D2 16681 virus and its attenuated D2 16681-PDK53 were constructed. The attenuated virus elicited neutralizing antibodies in mice and monkeys and developed viremia in monkeys. At molecular level, patterns of cytokines which are immunological mediators released from human mononuclear cells obtained from dengue naive and immune donors infected with this attenuated virus compared with virulent virus were studied. In dengue naive PBMC, the virulent and attenuated clones induced alternation in expression of 25 and 24 versus 13 and 18 genes out of 268 genes on day 1 and 3. In dengue immune PBMC, the virulent and attenuated clones induced alternation in expression of 33 and 38 versus 25 and 29 genes on days 1 and 3. Up-regulation of IL-1β, IL-6, IL-8, IL-10, IFN-α, IFNγR, MIP-1α, MIP-1β, MIP-2α, VEGF and down-regulation of IL-4, IL-4R, IL-RII, MIF, RANTES, IGF-1, GM-CSF-2 were shown. This review pointed out the infectious clones of the attenuated D2 16681-PDK53 was safe and induced both neutralizing antibodies in vivo and cytokine gene expression in vitro at molecular level. Furthermore, the phenotypic markers of ideal dengue vaccine could be included the alteration of cytokine gene expression and cytokine production in human mononuclear cells.
Export Options
About this article
Cite this article as:
Rabablert J. and Yoksan S., Attenuated D2 16681-PDK53 Vaccine: Defining Humoral and Cell- Mediated Immunity, Current Pharmaceutical Design 2009; 15 (11) . https://dx.doi.org/10.2174/138161209787846865
DOI https://dx.doi.org/10.2174/138161209787846865 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Epitope-Driven TB Vaccine Development: A Streamlined Approach Using Immuno-Informatics, ELISpot Assays, and HLA Transgenic Mice
Current Molecular Medicine Recent Advances in Synthesis of PAR Ligands as Therapeutic Strategy for Inflammatory Diseases
Mini-Reviews in Medicinal Chemistry The Immunoproteasome: An Emerging Therapeutic Target
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Rational Design of Antiviral Compounds)
Current Pharmaceutical Design First-in-Human Study of the Safety, Tolerability, Pharmacokinetics and - Preliminary Dynamics of Neuroprotectant 2-Iminobiotin in Healthy Subjects
Current Clinical Pharmacology The Role of Viruses in Neurodegenerative and Neurobehavioral Diseases
CNS & Neurological Disorders - Drug Targets Therapeutic Nucleic Acids
Recent Patents on Regenerative Medicine Neurological Effects of SARS-CoV-2 and Neurotoxicity of Antiviral Drugs Against COVID-19
Mini-Reviews in Medicinal Chemistry FMRI of the Emotions: Towards an Improved Understanding of Amygdala Function
Current Medical Imaging Recent Advances in the Development of Anti-Infective Prophylactic and/or Therapeutic Agents Based on Toll-Like Receptor (TLRs)
Recent Patents on Anti-Infective Drug Discovery New Perspectives in HCV Therapy: Entry Inhibitors
Recent Patents on Anti-Infective Drug Discovery Abnormal Functional and Structural Asymmetry as Biomarker for Schizophrenia
Current Topics in Medicinal Chemistry Cornea: Window to Ocular Immunology
Current Immunology Reviews (Discontinued) Trypanosomatid Parasites Causing Neglected Diseases
Current Medicinal Chemistry Inflammatory Risk Factors and Pathologies Associated with Alzheimers Disease
Current Alzheimer Research The Induction of Proinflammatory Cytokines in Response to Avian Influenza H5N1 Infections and their Role in Pathogenesis and the Enhancement of Virulence
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Development of High-throughput Identification and Heterologous Expression of Valuable Peptides/Proteins
Current Proteomics HIV-1 Capsid Inhibitors as Antiretroviral Agents
Current HIV Research Influenza and Stroke Risk: A Key Target Not to be Missed?
Infectious Disorders - Drug Targets Diversity in the Accessory Proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV Betacoronaviruses
Current Protein & Peptide Science