Current progress in dengue vaccines

Dengue is one of the most important emerging vector-borne viral diseases. There are four serotypes of dengue viruses (DENV), each of which is capable of causing self-limited dengue fever (DF) or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The major clinical manifestations of severe DENV disease are vascular leakage, thrombocytopenia, and hemorrhage, yet the detailed mechanisms are not fully resolved. Besides the direct effects of the virus, immunopathological aspects are also involved in the development of dengue symptoms. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, and live recombinant, DNA and subunit vaccines. The live attenuated virus vaccines and live chimeric virus vaccines are undergoing clinical evaluation. The other vaccine candidates have been evaluated in preclinical animal models or are being prepared for clinical trials. For the safety and efficacy of dengue vaccines, the immunopathogenic complications such as antibody-mediated enhancement and autoimmunity of dengue disease need to be considered.

[1]  A. Rothman.  Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms , 2011, Nature Reviews Immunology.

[2]  S. Green,et al.  Immunopathological mechanisms in dengue and dengue hemorrhagic fever , 2006, Current opinion in infectious diseases.

[3]  Saravudh Suvannadabba,et al.  Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial , 2012, The Lancet.

[4]  A. Barrett,et al.  17D yellow fever vaccines: new insights. A report of a workshop held during the World Congress on medicine and health in the tropics, Marseille, France, Monday 12 September 2005. , 2007, Vaccine.

[5]  A. Rothman,et al.  Bystander Target Cell Lysis and Cytokine Production by Dengue Virus-Specific Human CD4+ Cytotoxic T-Lymphocyte Clones , 1999, Journal of Virology.

[6]  M. Accavitti-Loper,et al.  Dengue virus neutralization by human immune sera: role of envelope protein domain III-reactive antibody. , 2009, Virology.

[7]  G. Screaton,et al.  Immunodominant T-cell responses to dengue virus NS3 are associated with DHF , 2010, Proceedings of the National Academy of Sciences.

[8]  B. M. Kaufman,et al.  Monoclonal antibodies against dengue 2 virus E-glycoprotein protect mice against lethal dengue infection. , 1987, The American journal of tropical medicine and hygiene.

[9]  I. Carletti,et al.  A Phase II, Randomized, Safety and Immunogenicity Study of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults , 2013, The American journal of tropical medicine and hygiene.

[10]  U. Braga-Neto,et al.  Alternative Complement Pathway Deregulation Is Correlated with Dengue Severity , 2009, PloS one.

[11]  Bjoern Peters,et al.  A Protective Role for Dengue Virus-Specific CD8+ T Cells 1 , 2009, The Journal of Immunology.

[12]  Yee‐Shin Lin,et al.  Deletion of the C-Terminal Region of Dengue Virus Nonstructural Protein 1 (NS1) Abolishes Anti-NS1-Mediated Platelet Dysfunction and Bleeding Tendency1 , 2009, The Journal of Immunology.

[13]  J. Sadoff,et al.  Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys. , 1996, The Journal of infectious diseases.

[14]  Yee‐Shin Lin,et al.  Factors contributing to the disturbance of coagulation and fibrinolysis in dengue virus infection. , 2013, Journal of the Formosan Medical Association = Taiwan yi zhi.

[15]  S. Green,et al.  Markers of dengue disease severity. , 2010, Current topics in microbiology and immunology.

[16]  D. Sujirarat,et al.  The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. , 2007, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[17]  P. Mason,et al.  Synergistic Interactions between the NS3hel and E Proteins Contribute to the Virulence of Dengue Virus Type 1 , 2012, PLoS neglected tropical diseases.

[18]  E. Konishi,et al.  Dengue type 2 virus subviral extracellular particles produced by a stably transfected mammalian cell line and their evaluation for a subunit vaccine. , 2002, Vaccine.

[19]  Luís Carlos de Souza Ferreira,et al.  Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant. , 2012, Vaccine.

[20]  A. Falconar,et al.  The dengue virus nonstructural-1 protein (NS1) generatesantibodies to common epitopes on human blood clotting,integrin/adhesin proteins and binds to humanendothelial cells: potential implications in haemorrhagic fever pathogenesis , 1997, Archives of Virology.

[21]  J. Lang,et al.  Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children , 2004, The Pediatric infectious disease journal.

[22]  Sophie Yacoub,et al.  The pathogenesis of dengue , 2013, Current opinion in infectious diseases.

[23]  J. Smit,et al.  Role of antibodies in controlling dengue virus infection. , 2009, Immunobiology.

[24]  P. Chong,et al.  A Novel Single-Dose Dengue Subunit Vaccine Induces Memory Immune Responses , 2011, PloS one.

[25]  E. Harris,et al.  Recent Advances in Deciphering Viral and Host Determinants of Dengue Virus Replication and Pathogenesis , 2006, Journal of Virology.

[26]  S. M. Costa,et al.  DNA vaccine against the non-structural 1 protein (NS1) of dengue 2 virus. , 2006, Vaccine.

[27]  J. Schlesinger,et al.  Synergistic interactions of anti-NS1 monoclonal antibodies protect passively immunized mice from lethal challenge with dengue 2 virus. , 1988, The Journal of general virology.

[28]  K. Morita,et al.  Dengue and Soluble Mediators of the Innate Immune System , 2011, Tropical medicine and health.

[29]  Steven A. Ogata,et al.  Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. , 2010, Vaccine.

[30]  Yee‐Shin Lin,et al.  Generation of IgM anti‐platelet autoantibody in dengue patients , 2001, Journal of medical virology.

[31]  D. Clements,et al.  The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease. , 2011, Vaccine.

[32]  Alan L Rothman,et al.  Dengue: defining protective versus pathologic immunity. , 2004, The Journal of clinical investigation.

[33]  S. Inoue,et al.  Association of increased platelet‐associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections , 2004, Clinical and experimental immunology.

[34]  D. Gubler,et al.  Dengue and dengue hemorrhagic fever. , 2014 .

[35]  Shuying Wang,et al.  Autoimmunity in dengue pathogenesis. , 2013, Journal of the Formosan Medical Association = Taiwan yi zhi.

[36]  B. Murphy,et al.  A Live, Attenuated Dengue Virus Type 1 Vaccine Candidate with a 30-Nucleotide Deletion in the 3′ Untranslated Region Is Highly Attenuated and Immunogenic in Monkeys , 2003, Journal of Virology.

[37]  S. M. Costa,et al.  DNA vaccines against dengue virus based on the ns1 gene: the influence of different signal sequences on the protein expression and its correlation to the immune response elicited in mice. , 2007, Virology.

[38]  A. Issekutz,et al.  Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes , 1997, Journal of virology.

[39]  E. Decroly,et al.  Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5. , 2007, Journal of molecular biology.

[40]  Yee‐Shin Lin,et al.  Molecular mimicry between virus and host and its implications for dengue disease pathogenesis , 2011, Experimental biology and medicine.

[41]  R. Padmanabhan,et al.  Processing and localization of Dengue virus type 2 polyprotein precursor NS3-NS4A-NS4B-NS5 , 1992, Journal of virology.

[42]  S. Inoue,et al.  Correlation between increased platelet‐associated IgG and thrombocytopenia in secondary dengue virus infections , 2003, Journal of medical virology.

[43]  J. Muñoz-Jordán,et al.  Inhibition of Alpha/Beta Interferon Signaling by the NS4B Protein of Flaviviruses , 2005, Journal of Virology.

[44]  T. Chambers,et al.  Neuroblastoma Cell-Adapted Yellow Fever 17D Virus: Characterization of a Viral Variant Associated with Persistent Infection and Decreased Virus Spread , 2002, Journal of Virology.

[45]  B. Guy,et al.  Innate and adaptive cellular immunity in flavivirus-naïve human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3). , 2006, Vaccine.

[46]  Angel Balmaseda,et al.  Dominant Cross-Reactive B Cell Response during Secondary Acute Dengue Virus Infection in Humans , 2012, PLoS neglected tropical diseases.

[47]  O. Horstick,et al.  Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries , 2011, BMC infectious diseases.

[48]  A. Veerman,et al.  Inflammatory Mediators in Dengue Virus Infection in Children: Interleukin-8 and Its Relationship to Neutrophil Degranulation , 2000, Infection and Immunity.

[49]  A. Rothman,et al.  Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection. , 2011, The Journal of infectious diseases.

[50]  V. Barban,et al.  High stability of yellow fever 17D-204 vaccine: a 12-year restrospective analysis of large-scale production. , 2007, Vaccine.

[51]  J. Lang,et al.  Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses. , 2002, The American journal of tropical medicine and hygiene.

[52]  Graham S. Ogg,et al.  Cellular and Cytokine Correlates of Severe Dengue Infection , 2012, PloS one.

[53]  Yee‐Shin Lin,et al.  Antibodies from dengue patient sera cross‐react with endothelial cells and induce damage , 2003, Journal of medical virology.

[54]  Tao Dong,et al.  Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever , 2003, Nature Medicine.

[55]  R. Houghten,et al.  Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection. , 1991, The Journal of infectious diseases.

[56]  J. Schlesinger,et al.  Immunization of mice with recombinant vaccinia virus expressing authentic dengue virus nonstructural protein NS1 protects against lethal dengue virus encephalitis , 1990, Journal of virology.

[57]  Sarah Murrell,et al.  Review of dengue virus and the development of a vaccine. , 2011, Biotechnology advances.

[58]  R. Rico-Hesse,et al.  Report of an NIAID workshop on dengue animal models. , 2010, Vaccine.

[59]  R. Rico-Hesse,et al.  Dengue Virus Structural Differences That Correlate with Pathogenesis , 1999, Journal of Virology.

[60]  Albert D. M. E. Osterhaus,et al.  Dengue Virus Pathogenesis: an Integrated View , 2009, Clinical Microbiology Reviews.

[61]  E. Harris,et al.  Protection from Secondary Dengue Virus Infection in a Mouse Model Reveals the Role of Serotype Cross-Reactive B and T Cells , 2012, The Journal of Immunology.

[62]  D. Burke,et al.  Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection. , 1989, The American journal of tropical medicine and hygiene.

[63]  R. Warren,et al.  Mice immunized with a dengue type 2 virus E and NS1 fusion protein made in Escherichia coli are protected against lethal dengue virus infection. , 1995, Vaccine.

[64]  S. Varga,et al.  Protective Heterologous Antiviral Immunity and Enhanced Immunopathogenesis Mediated by Memory T Cell Populations , 1998, The Journal of experimental medicine.

[65]  Juan Wang,et al.  Preliminary evaluation of DNA vaccine candidates encoding dengue-2 prM/E and NS1: their immunity and protective efficacy in mice. , 2013, Molecular immunology.

[66]  J. J. Greene,et al.  Purified dengue 2 virus envelope glycoprotein aggregates produced by baculovirus are immunogenic in mice. , 2000, Vaccine.

[67]  Y. S. Lin,et al.  Immunopathogenesis of dengue virus infection. , 2001, Journal of biomedical science.

[68]  M. Jacobs,et al.  Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction. , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[69]  P. Chong,et al.  A novel technology for the production of a heterologous lipoprotein immunogen in high yield has implications for the field of vaccine design. , 2009, Vaccine.

[70]  C. Huang,et al.  Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) formulations in interferon-deficient AG129 mice. , 2012, Vaccine.

[71]  J. Lang,et al.  Live-attenuated Tetravalent Dengue Vaccine in Dengue-naïve Children, Adolescents, and Adults in Mexico City: Randomized Controlled Phase 1 Trial of Safety and Immunogenicity , 2011, The Pediatric infectious disease journal.

[72]  D. Vaughn,et al.  Modification of dengue virus strains by passage in primary dog kidney cells: preparation of candidate vaccines and immunization of monkeys. , 2003, The American journal of tropical medicine and hygiene.

[73]  Shu-Fen Wu,et al.  Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice. , 2003, Vaccine.

[74]  R. Chanock,et al.  Dengue type 4 virus mutants containing deletions in the 3' noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys , 1996, Journal of virology.

[75]  B. Murphy,et al.  Prospects for a dengue virus vaccine , 2007, Nature Reviews Microbiology.

[76]  B. Seliger,et al.  Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. , 1998, Journal of immunology.

[77]  A. Nisalak,et al.  Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. , 2000, The Journal of infectious diseases.

[78]  S. H. Wang,et al.  The heterogeneous nuclear ribonucleoprotein K (hnRNP K) interacts with dengue virus core protein. , 2001, DNA and cell biology.

[79]  Robert Anderson,et al.  Dengue Virus Selectively Induces Human Mast Cell Chemokine Production , 2002, Journal of Virology.

[80]  M. Guzmán,et al.  Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris. , 2003, The American journal of tropical medicine and hygiene.

[81]  J. Lang,et al.  A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. , 2010, The Journal of infectious diseases.

[82]  J. Schlesinger,et al.  Protection of mice against dengue 2 virus encephalitis by immunization with the dengue 2 virus non-structural glycoprotein NS1. , 1987, The Journal of general virology.

[83]  P. Yenchitsomanus,et al.  Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis. , 2010, Virus research.

[84]  E. Harris,et al.  Antibodies targeting dengue virus envelope domain III are not required for serotype-specific protection or prevention of enhancement in vivo. , 2012, Virology.

[85]  L. Lazo,et al.  The cellular immune response plays an important role in protecting against dengue virus in the mouse encephalitis model. , 2009, Viral immunology.

[86]  L. Sexton.  The Treatment of Yellow Fever , 1903, The Indian medical gazette.

[87]  T. Yasumoto,et al.  Ciguatera fish poisoning on Kakeroma Island, Kagoshima Prefecture, Japan. , 2011 .

[88]  Yee‐Shin Lin,et al.  Dengue Vaccines: Challenge and Confrontation , 2011 .

[89]  P. Niyomrattanakit,et al.  Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation , 2004, Journal of Virology.

[90]  A. Kroeger,et al.  Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever , 2006, Tropical medicine & international health : TM & IH.

[91]  K. Pierce,et al.  Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. , 2011, Vaccine.

[92]  J. Lang,et al.  Live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: randomized controlled phase I trial in the Philippines. , 2011, Vaccine.

[93]  Adolfo García-Sastre,et al.  Inhibition of interferon signaling by dengue virus , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  A. Nisalak,et al.  Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. , 1991, The Journal of clinical investigation.

[95]  M. Diamond,et al.  N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement. , 2011, Virology.

[96]  P. Glaziou,et al.  Correlation between detection of plasminogen cross-reactive antibodies and hemorrhage in dengue virus infection. , 1994, The Journal of infectious diseases.

[97]  V. Stollar,et al.  Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization. , 1989, Virology.

[98]  B. Murphy,et al.  Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity. , 2008, The American journal of tropical medicine and hygiene.

[99]  R. Padmanabhan,et al.  De Novo Synthesis of RNA by the Dengue Virus RNA-dependent RNA Polymerase Exhibits Temperature Dependence at the Initiation but Not Elongation Phase* , 2001, The Journal of Biological Chemistry.

[100]  B. Murphy,et al.  Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Δ30 with those of DEN1 , 2007, Virology Journal.

[101]  G. Maga,et al.  The RNA helicase, nucleotide 5'-triphosphatase, and RNA 5'-triphosphatase activities of Dengue virus protein NS3 are Mg2+-dependent and require a functional Walker B motif in the helicase catalytic core. , 2004, Virology.

[102]  R. Chanock,et al.  Proper processing of dengue virus nonstructural glycoprotein NS1 requires the N-terminal hydrophobic signal sequence and the downstream nonstructural protein NS2a , 1989, Journal of virology.

[103]  Suresh Mahalingam,et al.  Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes , 2010, The Lancet Infectious Diseases.

[104]  A. Sampath,et al.  Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. , 2006, The Journal of general virology.

[105]  A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates , 2013, Archives of Virology.

[106]  M. Guzmán,et al.  A recombinant fusion protein containing the domain III of the dengue-2 envelope protein is immunogenic and protective in nonhuman primates. , 2006, Vaccine.

[107]  R. Edelman,et al.  Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates. , 2003, The American journal of tropical medicine and hygiene.

[108]  S. Swaminathan,et al.  Replication-Defective Adenoviral Vaccine Vector for the Induction of Immune Responses to Dengue Virus Type 2 , 2003, Journal of Virology.

[109]  D. Vaughn,et al.  An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model. , 2005, Vaccine.

[110]  M. Guzmán,et al.  Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice. , 2009, International immunology.

[111]  F. Guirakhoo,et al.  Safety and Efficacy of Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine Formulations in Nonhuman Primates , 2004, Journal of Virology.

[112]  Rosanna W. Peeling,et al.  Dengue: a continuing global threat , 2010, Nature Reviews Microbiology.

[113]  J. An,et al.  Dengue-specific CD8+ T cells have both protective and pathogenic roles in dengue virus infection. , 2004, Immunology letters.

[114]  R. Schlesinger,et al.  Dengue Viruses , 1977, Virology Monographs Die Virusforschung in Einzeldarstellungen.

[115]  J. Lepault,et al.  Dengue Virus Type 1 Nonstructural Glycoprotein NS1 Is Secreted from Mammalian Cells as a Soluble Hexamer in a Glycosylation-Dependent Fashion , 1999, Journal of Virology.

[116]  Cameron P Simmons,et al.  The pathogenesis of dengue. , 2011, Vaccine.

[117]  K. Morita,et al.  Molecular evolution, distribution and genetic relationship among the dengue 2 viruses isolated from different clinical severity. , 2000, The Southeast Asian journal of tropical medicine and public health.

[118]  Yee‐Shin Lin,et al.  The Dual-Specific Binding of Dengue Virus and Target Cells for the Antibody-Dependent Enhancement of Dengue Virus Infection1 , 2006, The Journal of Immunology.

[119]  B. Murphy,et al.  Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2 , 2004, BMC infectious diseases.

[120]  Yee‐Shin Lin,et al.  Autoimmune pathogenesis in dengue virus infection. , 2006, Viral immunology.

[121]  Lauren E. Yauch,et al.  Mouse models of dengue virus infection and disease. , 2008, Antiviral research.

[122]  S. Halstead,et al.  How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections , 2010, Clinical and Vaccine Immunology.

[123]  Cameron P. Simmons,et al.  Current concepts: Dengue , 2012 .

[124]  M. Rossmann,et al.  Molecular mechanisms involved in the early steps of flavivirus cell entry. , 2011, Microbes and infection.

[125]  S. Kalayanarooj,et al.  Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. , 2010, The Journal of infectious diseases.

[126]  R. Rico-Hesse,et al.  American Genotype Structures Decrease Dengue Virus Output from Human Monocytes and Dendritic Cells , 2003, Journal of Virology.

[127]  A. Davidson,et al.  Mutagenesis of the Dengue Virus Type 2 NS3 Protein within and outside Helicase Motifs: Effects on Enzyme Activity and Virus Replication , 2001, Journal of Virology.

[128]  A. Rothman,et al.  Altered Cytokine Responses of Dengue-Specific CD4+ T Cells to Heterologous Serotypes 1 , 2005, The Journal of Immunology.

[129]  Alfonso Gúzman,et al.  Update on the global spread of dengue. , 2010, International journal of antimicrobial agents.

[130]  B. Murphy,et al.  Genetically modified, live attenuated dengue virus type 3 vaccine candidates. , 2004, The American journal of tropical medicine and hygiene.

[131]  Stephen J. Thomas,et al.  Critical issues in dengue vaccine development , 2011, Current opinion in infectious diseases.

[132]  A. D. de Silva,et al.  The Human Antibody Response to Dengue Virus Infection , 2011, Viruses.

[133]  M. Blettner,et al.  Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. , 2006, The Journal of infectious diseases.

[134]  Cameron P. Simmons,et al.  An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection , 2010, Journal of Virology.

[135]  A. Yueh,et al.  A novel dengue vaccine candidate that induces cross-neutralizing antibodies and memory immunity. , 2009, Microbes and infection.

[136]  Ralf Bartenschlager,et al.  Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites , 2009, Cell Host & Microbe.

[137]  S. Halstead,et al.  Dengue vaccine development: a 75% solution? , 2012, The Lancet.

[138]  J. Chin,et al.  The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry. , 2007, Microbes and infection.

[139]  T. Kinoshita,et al.  Association of dengue virus NS1 protein with lipid rafts. , 2008, The Journal of general virology.

[140]  B. Moss,et al.  Immunization of rhesus monkeys with a recombinant of modified vaccinia virus Ankara expressing a truncated envelope glycoprotein of dengue type 2 virus induced resistance to dengue type 2 virus challenge. , 2000, Vaccine.

[141]  T. Peng,et al.  The Animal Models for Dengue Virus Infection , 2004 .

[142]  B. Murphy,et al.  Immune response to dengue virus and prospects for a vaccine. , 2011, Annual review of immunology.

[143]  A. Falconar.  Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design , 2007, Clinical and Vaccine Immunology.

[144]  S. Halstead,et al.  Neutralization and antibody-dependent enhancement of dengue viruses. , 2003, Advances in virus research.

[145]  N. Bhamarapravati,et al.  Live attenuated tetravalent dengue vaccine. , 2000, Vaccine.