344
Views
8
CrossRef citations to date
0
Altmetric
Review

Aiming at the heart: the capsid protein of dengue virus as a vaccine candidate

, , , &
Pages 161-173 | Received 26 Nov 2018, Accepted 23 Jan 2019, Published online: 11 Feb 2019

References

  • Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013 Apr 25;496(7446):504–507.
  • Sabchareon A, Wallace D, Sirivichayakul C, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012 Nov 3;380(9853):1559–1567.
  • Villar L, Dayan GH, Arredondo-Garcia JL, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015 Jan 8;372(2):113–123.
  • Capeding MR, Tran NH, Hadinegoro SR, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet. 2014;384(9951):1358–1365.
  • van der Most RG, Murali-Krishna K, Ahmed R, et al. Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response. J Virol. 2000 Sep;74(17):8094–8101.
  • van der Most RG, Murali-Krishna K, Ahmed R. Prolonged presence of effector-memory CD8 T cells in the central nervous system after dengue virus encephalitis. Int Immunol. 2003 Jan;15(1):119–125.
  • Yauch LE, Zellweger RM, Kotturi MF, et al. A protective role for dengue virus-specific CD8+ T cells. J Immunol. 2009 Apr 15;182(8):4865–4873.
  • Weiskopf D, Angelo MA, de Azeredo EL, et al. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells. Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2046–E2053.
  • Weiskopf D, Angelo MA, Bangs DJ, et al. The human CD8+ T cell responses induced by a live attenuated tetravalent dengue vaccine are directed against highly conserved epitopes. J Virol. 2015 Jan 1;89(1):120–128.
  • Guzman MG, Hermida L, Bernardo L, et al. Domain III of the envelope protein as a dengue vaccine target. Expert Rev Vaccines. 2010 Feb;9(2):137–147.
  • Ma L, Jones CT, Groesch TD, et al. Solution structure of dengue virus capsid protein reveals another fold. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3414–3419.
  • Markoff L, Falgout B, Chang A. A conserved internal hydrophobic domain mediates the stable membrane integration of the dengue virus capsid protein. Virology. 1997 Jun 23;233(1):105–117.
  • Jones CT, Ma L, Burgner JW, et al. Flavivirus capsid is a dimeric alpha-helical protein. J Virol. 2003 Jun;77(12):7143–7149.
  • Byk LA, Gamarnik AV. Properties and functions of the dengue virus capsid protein. Annu Rev Virol. 2016 Sep 29;3(1):263–281.
  • Oliveira ERA, Mohana-Borges R, de Alencastro RB, et al. The flavivirus capsid protein: structure, function and perspectives towards drug design. Virus Res. 2017 Jan;2(227):115–123.
  • Westaway EG, Khromykh AA, Kenney MT, et al. Proteins C and NS4B of the flavivirus Kunjin translocate independently into the nucleus. Virology. 1997 Jul 21;234(1):31–41.
  • Wang SH, Syu WJ, Huang KJ, et al. Intracellular localization and determination of a nuclear localization signal of the core protein of dengue virus. J Gen Virol. 2002 Dec;83(Pt 12):3093–3102.
  • Takimoto M, Tomonaga T, Matunis M, et al. Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J Biol Chem. 1993 Aug 25;268(24):18249–18258.
  • Airo AM, Urbanowski MD, Lopez-Orozco J, et al. Expression of flavivirus capsids enhance the cellular environment for viral replication by activating Akt-signalling pathways. Virology. 2018 Mar;516:147–157.
  • Kumar R, Singh N, Abdin MZ, et al. Dengue virus capsid interacts with DDX3X-A potential mechanism for suppression of antiviral functions in dengue infection. Front Cell Infect Microbiol. 2017;7:542.
  • Gagnon SJ, Zeng W, Kurane I, et al. Identification of two epitopes on the dengue 4 virus capsid protein recognized by a serotype-specific and a panel of serotype-cross-reactive human CD4+ cytotoxic T-lymphocyte clones. J Virol. 1996 Jan;70(1):141–147.
  • Weiskopf D, Angelo MA, Grifoni A, et al. HLA-DRB1 alleles are associated with different magnitudes of dengue virus-specific CD4+ T-cell responses. J Infect Dis. 2016 Oct 1;214(7):1117–1124.
  • Anandarao R, Swaminathan S, Khanna N. The identification of immunodominant linear epitopes of dengue type 2 virus capsid and NS4a proteins using pin-bound peptides. Virus Res. 2005 Sep;112(1–2):60–68.
  • Nadugala MN, Jeewandara C, Malavige GN, et al. Natural antibody responses to the capsid protein in sera of Dengue infected patients from Sri Lanka. PLoS One. 2017;12(6):e0178009.
  • Mongkolsapaya J, Duangchinda T, Dejnirattisai W, et al. T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal? J Immunol. 2006 Mar 15;176(6):3821–3829.
  • Friberg H, Bashyam H, Toyosaki-Maeda T, et al. Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans. Sci Rep. 2011;1.
  • Mongkolsapaya J, Dejnirattisai W, Xu XN, et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med. 2003 Jul;9(7):921–927.
  • Zellweger RM, Eddy WE, Tang WW, et al. CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice. J Immunol. 2014 Oct 15;193(8):4117–4124.
  • Zellweger RM, Tang WW, Eddy WE, et al. CD8+ T cells can mediate short-term protection against heterotypic dengue virus reinfection in mice. J Virol. 2015 Jun 15;89(12):6494–6505.
  • Khromykh A, Westaway EG. RNA binding properties of core protein of the flavivirus Kunjin. Arch Virol. 1996;141(3–4):685–699.
  • Khan AM, Heiny AT, Lee KX, et al. Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus. BMC Bioinformatics. 2006;7(Suppl 5):S4.
  • Khan AM, Miotto O, Nascimento EJ, et al. Conservation and variability of dengue virus proteins: implications for vaccine design. PLoS Negl Trop Dis. 2008;2(8):e272.
  • Lam JH, Ong LC, Alonso S. Key concepts, strategies, and challenges in dengue vaccine development: an opportunity for sub-unit candidates? Expert Rev Vaccines. 2016 Apr;15(4):483–495.
  • Guy B, Noriega F, Ochiai RL, et al. A recombinant live attenuated tetravalent vaccine for the prevention of dengue. Expert Rev Vaccines. 2017 Jul;16(7):1–13.
  • Whitehead SS. Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD vaccine? Expert Rev Vaccines. 2016 Apr;15(4):509–517.
  • Osorio JE, Wallace D, Stinchcomb DT. A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone. Expert Rev Vaccines. 2016 Apr;15(4):497–508.
  • Fernandez S, Thomas SJ, De La Barrera R, et al. An adjuvanted, tetravalent dengue virus-purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques. Am J Trop Med Hyg. 2015 Feb 2.
  • Khetarpal N, Khanna I. Dengue Fever: causes, Complications, and Vaccine Strategies. J Immunol Res. 2016;2016:6803098.
  • Bauer K, Esquilin IO, Cornier AS, et al. A phase II, randomized, safety and immunogenicity trial of a re-derived, live-attenuated dengue virus vaccine in healthy children and adults living in puerto rico. Am J Trop Med Hyg. 2015 Sep;93(3):441–453.
  • Manoff SB, Sausser M, Russell AF, et al. Immunogenicity and safety of an investigational tetravalent recombinant subunit vaccine for dengue: results of a Phase I randomized clinical trial in flavivirus-Naive adults. Hum Vaccin Immunother. 2018 Nov 14.
  • Sullivan SM, Doukas J, Hartikka J, et al. Vaxfectin: a versatile adjuvant for plasmid DNA- and protein-based vaccines. Expert Opin Drug Deliv. 2010 Dec;7(12):1433–1446.
  • Danko JR, Kochel T, Teneza-Mora N, et al. Safety and immunogenicity of a tetravalent dengue DNA vaccine administered with a cationic lipid-based adjuvant in a phase 1 clinical trial. Am J Trop Med Hyg. 2018 Mar;98(3):849–856.
  • Remakus S, Sigal LJ. Memory CD8(+) T cell protection. Adv Exp Med Biol. 2013;785:77–86.
  • Sant AJ, McMichael A. Revealing the role of CD4(+) T cells in viral immunity. J Exp Med. 2012 Jul 30;209(8):1391–1395.
  • Rivino L. T cell immunity to dengue virus and implications for vaccine design. Expert Rev Vaccines. 2016 Apr;15(4):443–453.
  • Kurane I, Meager A, Ennis FA. Dengue virus-specific human T cell clones Serotype crossreactive proliferation, interferon gamma production, and cytotoxic activity. J Exp Med. 1989 Sep 1;170(3):763–775.
  • Mathew A, Kurane I, Rothman AL, et al. Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a. J Clin Invest. 1996 Oct 1;98(7):1684–1691.
  • Gagnon SJ, Ennis FA, Rothman AL. Bystander target cell lysis and cytokine production by dengue virus-specific human CD4(+) cytotoxic T-lymphocyte clones. J Virol. 1999 May;73(5):3623–3629.
  • Livingston PG, Toomey S, Kurane I, et al. Modulation of the functions of dengue virus-specific human CD8+ cytotoxic T cell clone by IL-2, IL-7 and IFN gamma. Immunol Invest. 1995 May;24(4):619–629.
  • Hatch S, Endy TP, Thomas S, et al. Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection. J Infect Dis. 2011 May;203(9):1282–1291.
  • Gunther VJ, Putnak R, Eckels KH, et al. A human challenge model for dengue infection reveals a possible protective role for sustained interferon gamma levels during the acute phase of illness. Vaccine. 2011 May 17;29(22):3895–3904.
  • Rivino L, Kumaran EA, Jovanovic V, et al. Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection. J Virol. 2013 Mar;87(5):2693–2706.
  • Lindow JC, Borochoff-Porte N, Durbin AP, et al. Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans. PLoS Negl Trop Dis. 2012;6(7):e1742.
  • Weiskopf D, Bangs DJ, Sidney J, et al. Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4256–E4263.
  • Jeewandara C, Adikari TN, Gomes L, et al. Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. PLoS Negl Trop Dis. 2015 Apr;9(4):e0003673.
  • Lazo L, Hermida L, Zulueta A, et al. A recombinant capsid protein from dengue-2 induces protection in mice against homologous virus. Vaccine. 2007 Jan 22;25(6):1064–1070.
  • Lopez C, Gil L, Lazo L, et al. In vitro assembly of nucleocapsid-like particles from purified recombinant capsid protein of dengue-2 virus. Arch Virol. 2009;154(4):695–698.
  • Wengler G, Wengler G, Boege U, et al. Establishment and analysis of a system which allows assembly and disassembly of alphavirus core-like particles under physiological conditions in vitro. Virology. 1984 Jan 30;132(2):401–412.
  • Gil L, Bernardo L, Pavon A, et al. Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cell-mediated immunity in mice. J Gen Virol. 2012 Jun;93(Pt 6):1204–1214.
  • Lazo L, Gil L, Lopez C, et al. Nucleocapsid-like particles of dengue-2 virus enhance the immune response against a recombinant protein of dengue-4 virus. Arch Virol. 2010 Oct;155(10):1587–1595.
  • Lazo L, Gil L, Lopez C, et al. A vaccine formulation consisting of nucleocapsid-like particles from dengue-2 and the fusion protein P64k-domain III from Dengue-1 induces a protective immune response against the homologous serotypes in mice. Acta Trop. 2012 Nov;124(2):107–112.
  • Riedl P, Stober D, Oehninger C, et al. Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain. J Immunol. 2002 May 15;168(10):4951–4959.
  • Donnelly J, Berry K, Ulmer JB. Technical and regulatory hurdles for DNA vaccines. Int J Parasitol. 2003 May;33(5–6):457–467.
  • Suzarte E, Marcos E, Gil L, et al. Generation and characterization of potential dengue vaccine candidates based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. Arch Virol. 2014 Jul;159(7):1629–1640.
  • Gil L, Marcos E, Izquierdo A, et al. The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV-2. Immunol Cell Biol. 2015 Jan;93(1):57–66.
  • Chaung HC. CpG oligodeoxynucleotides as DNA adjuvants in vertebrates and their applications in immunotherapy. Int Immunopharmacol. 2006 Oct;6(10):1586–1596.
  • Gil L, Cobas K, Lazo L, et al. A tetravalent formulation based on recombinant nucleocapsid-like particles from dengue viruses induces a functional immune response in mice and monkeys. J Immunol. 2016;197(9):3597–3606.
  • Suzarte E, Gil L, Valdes I, et al. A novel tetravalent formulation combining the four aggregated domain III-capsid proteins from dengue viruses induces a functional immune response in mice and monkeys. Int Immunol. 2015 Mar 20.
  • Gil L, Lazo L, Valdes I, et al. The tetravalent formulation of domain III-capsid proteins recalls memory B- and T-cell responses induced in monkeys by an experimental dengue virus infection. Clin Transl Immunology. 2017 Jun;6(6):e148.
  • Gil L, Lopez C, Lazo L, et al. Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice. Int Immunol. 2009;21(10):1175–1183.
  • Valdes I, Bernardo L, Gil L, et al. A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. Virology. 2009 Nov 25;394(2):249–258.
  • Izquierdo A, Valdes I, Gil L, et al. Serotype specificity of recombinant fusion protein containing domain III and capsid protein of dengue virus 2. Antiviral Res. 2012 Jul;95(1):1–8.
  • Marcos E, Gil L, Lazo L, et al. Purified and highly aggregated chimeric protein DIIIC-2 induces a functional immune response in mice against dengue 2 virus. Arch Virol. 2013 Jan;158(1):225–230.
  • Marcos E, Gil L, Izquierdo A, et al. A dose-response study in mice of the vaccine preparation containing the diiic-2 protein aggregated with the oligodeoxinucleotide 39m. Bionatura. 2015;1(1):4–19.
  • Zust R, Toh YX, Valdes I, et al. Type I interferon signals in macrophages and dendritic cells control dengue virus infection: implications for a new mouse model to test dengue vaccines. J Virol. 2014 Jul 1;88(13):7276–7285.
  • Zust R, Valdes I, Skibinski D, et al. Tetravalent dengue DIIIC protein together with alum and ODN elicits a Th1 response and neutralizing antibodies in mice. Vaccine. 2015 Mar 17;33(12):1474–1482.
  • Gil L, Izquierdo A, Lazo L, et al. Capsid protein: evidences about the partial protective role of neutralizing antibody-independent immunity against dengue in monkeys. Virology. 2014;456–457:70–76.
  • Valdes I, Marcos E, Suzarte E, et al. A dose-response study in mice of a tetravalent vaccine candidate composed of domain III-capsid proteins from dengue viruses. Arch Virol. 2017 Aug;162(8):2247–2256.
  • Lazo VL, Gil GL, Marcos LE, et al. Evaluation in mice of the immunogenicity of a tetravalent subunit vaccine candidate against dengue virus using mucosal and parenteral immunization routes. Viral Immunol. 2017 Jun;30(5):350–358.
  • Valdes I, Gil L, Romero Y, et al. The chimeric protein domain III-capsid of dengue virus serotype 2 (DEN-2) successfully boosts neutralizing antibodies generated in monkeys upon infection with DEN-2. Clin Vaccine Immunol. 2011 Mar;18(3):455–459.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.