• 1.

    Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI, 2013. The global distribution and burden of dengue. Nature 496: 504507.

    • Search Google Scholar
    • Export Citation
  • 2.

    Nisalak A, Endy TP, Nimmannitya S, Kalayanarooj S, Thisayakorn U, Scott RM, Burke DS, Hoke CH, Innis BL, Vaughn DW, 2003. Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999. Am J Trop Med Hyg 68: 191202.

    • Search Google Scholar
    • Export Citation
  • 3.

    World Health Organization (WHO), 2012. Dengue and Severe Dengue Fact Sheet #117. Available at: http://www.who.int/mediacentre/factsheets/fs117/en/index.html. Accessed February 27, 2013.

    • Search Google Scholar
    • Export Citation
  • 4.

    Wichmann O, Yoon I-K, Vong S, Limkittikul K, Gibbons RV, Mammen MP, Ly S, Buchy P, Sirivichayakul C, Buathong R, Huy R, Letson GW, Sabchareon A, 2011. PLOS Neglected Tropical Diseases Dengue in Thailand and Cambodia: An Assessment of the Degree of Underrecognized Disease Burden Based on Reported Cases. Available at: http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000996. Accessed February 27, 2013.

    • Search Google Scholar
    • Export Citation
  • 5.

    Innis BL, Eckels KH, 2003. Progress in development of a live attenuated, tetravalent dengue virus vaccine by the United States Army Medical Research and Materiel Command. Am J Trop Med Hyg 69: 14.

    • Search Google Scholar
    • Export Citation
  • 6.

    Edelman R, Wasserman SS, Bodison SA, Putnak RJ, Eckels KH, Tang D, Kanesa-Thasan N, Vaughn DW, Innis BL, Sun W, 2003. Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine. Am J Trop Med Hyg 69 (Suppl): 4860.

    • Search Google Scholar
    • Export Citation
  • 7.

    Sun W, Cunningham D, Wasserman SS, Perry J, Putnak JR, Eckels KH, Vaughn DW, Thomas SJ, Kanesa-Thasan N, Innis BL, Edelman R, 2009. Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naïve adults. Hum Vaccin 5: 3340.

    • Search Google Scholar
    • Export Citation
  • 8.

    Simasathien S, Thomas SJ, Watanaveeradej V, Nisalak A, Barberousse C, Innis BL, Sun W, Putnak RJ, Eckels KH, Hutagalung Y, Gibbons RV, Zhang C, De La Barrera R, Jarman RG, Chawachalasai W, Mammen MP Jr, 2008. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus naïve children. Am J Trop Med Hyg 78: 426433.

    • Search Google Scholar
    • Export Citation
  • 9.

    Watanaveeradej V, Simasathien S, Nisalak A, Endy TP, Jarman RG, Innis BL, Thomas SJ, Gibbons RV, Hengprasert S, Samakoses R, Kerdpanich A, Vaughn DW, Putnak JR, Eckels KH, Barrera R de L, Mammen MP Jr, 2011. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants. Am J Trop Med Hyg 85: 341351.

    • Search Google Scholar
    • Export Citation
  • 10.

    Thomas SJ, Eckels KH, Carletti I, De La Barrera R, Dessy F, Fernandez S, Putnak R, Toussaint JF, Sun W, Bauer K, Gibbons RV, Innis BL, 2013. A phase II, randomized, safety and immunogenicity study of a re-derived, live-attenuated dengue virus vaccine in healthy adults. Am J Trop Med Hyg 88: 7388.

    • Search Google Scholar
    • Export Citation
  • 11.

    Medical Dictionary for Regulatory Activities. International Committee on Harmonization. Available at: http://www.meddramsso.com. Accessed January 2, 2014.

    • Search Google Scholar
    • Export Citation
  • 12.

    Lee IK, Lee WH, Liu JW, Yang KD, 2010. Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients. Int J Infect Dis 14: e919e922.

    • Search Google Scholar
    • Export Citation
  • 13.

    Sadon N, Delers A, Jarman RG, Klungthong C, Nisalak A, Gibbons RV, Vassilev V, 2008. A new quantitative RT-PCR method for sensitive detection of dengue virus in serum samples. J Virol Methods 153: 16.

    • Search Google Scholar
    • Export Citation
  • 14.

    Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Rothman AL, Ennis FA, Nisalak A, 1997. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis 176: 322330.

    • Search Google Scholar
    • Export Citation
  • 15.

    Beckett CG, Kosasih H, Faisal I, Nurhayati, Tan R, Widjaja S, Listiyaningsih E, Ma'roef C, Wuryadi S, Bangs MJ, Samsi TK, Yuwono D, Hayes CG, Porter KR, 2005. Early detection of dengue infections using cluster sampling around index cases. Am J Trop Med Hyg 72: 777782.

    • Search Google Scholar
    • Export Citation
  • 16.

    Thai KT, Nishiura H, Hoang PL, Tran NT, Phan GT, Le HQ, Tran BQ, Nguyen NV, de Vries PJ, 2011. Age-specificity of clinical dengue during primary and secondary infections. PLoS Negl Trop Dis 5: e1180.

    • Search Google Scholar
    • Export Citation
  • 17.

    Yoon IK, Rothman AL, Tannitisupawong D, Srikiatkhachorn A, Jarman RG, Aldstadt J, Nisalak A, Mammen MP Jr, Thammapalo S, Green S, Libraty DH, Gibbons RV, Getis A, Endy T, Jones JW, Koenraadt CJ, Morrison AC, Fansiri T, Pimgate C, Scott TW, 2012. Underrecognized mildly symptomatic viremic dengue virus infections in rural Thai schools and villages. J Infect Dis 206: 389398.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gregory CJ, Lorenzi OD, Colón L, García AS, Santiago LM, Rivera RC, Bermúdez LJ, Báez FO, Aponte DV, Tomashek KM, Gutierrez J, Alvarado L, 2011. Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room. PLoS Negl Trop Dis 5: e1400.

    • Search Google Scholar
    • Export Citation
  • 19.

    Halstead SB, 2013. Dengue vascular permeability syndrome: what, no T cells? Clin Infect Dis 56: 900901.

  • 20.

    Capeding RZ, Luna IA, Bomasang E, Lupisan S, Lang J, Forrat R, Wartel A, Crevat D, 2011. Live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: randomized controlled phase I trial in the Philippines. Vaccine 29: 38633872.

    • Search Google Scholar
    • Export Citation
  • 21.

    Sangkawibha N, Rojanasuphot S, Ahandrik S, Viriyapongse S, Jatanasen S, Salitul V, Phanthumachinda B, Halstead SB, 1984. Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol 120: 653669.

    • Search Google Scholar
    • Export Citation
  • 22.

    Guzmán MG, Kourí G, Martínez E, Bravo J, Riverón R, Soler M, Vázquez S, Morier L, 1987. Clinical and serologic study of Cuban children with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Bull Pan Am Health Organ 21: 270279.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

Safety and Immunogenicity of a Rederived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults Living in Thailand: A Randomized Trial

View More View Less
  • Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; US Army Medical Component–Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Vaccines, Wavre, Belgium; Bioproduction Facility, Translational Medicine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania

Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial (NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.

Author Notes

* Address correspondence to Stephen J. Thomas, Viral Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910. E-mail: stephen.j.thomas3.mil@mail.mil† These authors contributed equally.

Financial support: This work was funded by US Army Medical Research and Materiel Command (Fort Detrick, MD) and GlaxoSmithKline Biologicals SA (Rixensart, Belgium) under a Cooperative Research and Development Agreement. GlaxoSmithKline Biologicals SA was involved in all stages of study conduct, including analysis of the data, and also took in all costs associated with the development and publication of this manuscript.

Authors' addresses: Veerachai Watanaveeradej, Sriluck Simasathien, and Angkool Kerdpanich, Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand, E-mails: veerachaiw@yahoo.com, ssriluck@hotmail.com, and akpmk@yahoo.com. Robert V. Gibbons, Research Directorate, Statistics and Epidemiology, US Army Institute of Surgical Research (USAISR), JBSA Ft. Sam Houston, TX, E-mail: robert.v.gibbons2.mil@mail.mil. Ananda Nisalak, Department of Virology, US Army Medical Component–Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mail: anandan@afrims.org. Richard G. Jarman and Stephen J. Thomas, Viral Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: rick.jarman@us.army.mil and stephen.thomas@amedd.army.mil. Elodie Tournay, GlaxoSmithKline Vaccines, Vaccine Value and Health Science, Biomedical Data Sciences, Wavre, Belgium, E-mail: elodie.x.tournay@gsk.com. Rafael De La Barrerra and Kenneth H. Eckels, Translational Medicine Branch, Pilot Bioproduction Facility, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: rafael.delabarrera@amedd.army.mil and kenneth.eckels@amedd.army.mil. Francis Dessy, GlaxoSmithKline Vaccines, Vaccine Discovery and Development, Viral Functional Immunology, Wavre, Belgium, E-mail: francis.dessy@gsk.com. Jean-François Toussaint, GlaxoSmithKline Vaccines, Vaccine Discovery and Development, Viral Disease Area Program, Rixensart, Belgium, E-mail: jean-francois.x.toussaint@gsk.com. Bruce L. Innis, GlaxoSmithKline Vaccines, King of Prussia, PA, E-mail: bruce.2.innis@gsk.com.

Save