VACCINATION OF HUMAN VOLUNTEERS WITH MONOVALENT AND TETRAVALENT LIVE-ATTENUATED DENGUE VACCINE CANDIDATES

WELLINGTON SUN Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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ROBERT EDELMAN Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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NIRANJAN KANESA-THASAN Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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KENNETH H. ECKELS Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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J. ROBERT PUTNAK Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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ALAN D. KING Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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HUO-SHU HOUNG Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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DOUGLAS TANG Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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JOHN M. SCHERER Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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CHARLES H. HOKE JR. Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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BRUCE L. INNIS Department of Virus Diseases, Department of Biologics Research, and Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Military Infectious Disease Research Program, United States Army Medical Research and Materiels Command, Fort Detrick, Frederick, Maryland

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Four serotypes of monovalent live attenuated dengue virus vaccine candidates were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers. The four monovalent candidates were then combined into a tetravalent formulation and given to another 10 volunteers. Neutralizing antibody seroconversion rates after a single-dose monovalent vaccination ranged from 53% to 100%. Solicited reactogenicity was scored by each volunteer. A composite index, the Reactogenicity Index, was derived by these self-reported scores. Reactogenicity differed among the four serotype candidates with serotype-1 associated with the most vaccine related side effects. A second dose of monovalent vaccines at either 30 days or 90 days was much less reactogenic but did not significantly increase seroconversion rates. Seroconversion rates in the 10 volunteers who received a single dose of tetravalent vaccine ranged from 30% to 70% among the four serotypes. Similar to the monovalent vaccines, a second dose of the tetravalent vaccine at one month was less reactogenic and did not increase seroconversion. A third dose of the tetravalent vaccine at four months resulted in three of four volunteers with trivalent or tetravalent high-titer neutralizing antibody responses.

  • 1

    Sabin AB, 1959. Viral and Rickettsial Infections of Man. Third edition. Philadelphia: J. B. Lippincott Company, 361.

  • 2

    Burke DS, Nisalak A, Mohnson DE, Scott RM, 1988. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 38 :172–180.

  • 3

    Winter PE, Yuill TM, Udomsakdi S, Gould D, Nantapanich S, Russell PK, 1968. An insular outbreak of dengue hemorrhagic fever. Am J Trop Med Hyg 17 :590–599.

    • Search Google Scholar
    • Export Citation
  • 4

    World Health Organization, 2002. The Fifty-fifth World Health Assembly of the WHO Resolution WHA55.17 on Dengue Fever and Dengue Hemorrhagic Fever Prevention and Control. Geneva: World Health Organization, May 18, 2002.

  • 5

    Halstead SB, 1978. Studies on the attenuation of dengue 4. Asian J Infect Dis 2 :112–117.

  • 6

    Bhamarapravati N, Yoksan S, 1997. Live attenuated dengue tetravalent vaccine. Gubler DJ, Kuno G, eds. Dengue and Dengue Hemorrhagic Fever. New York: CAB International, 367–377.

  • 7

    Kanesa-thasan N, Sun W, Kim-Ahn G, Van Albert S, Putnak JR, King A, Raengsakulsrach B, Christ-Schmidt H, Gilson K, Zahradnik JM, Vaughn DW, Innis BL, Saluzzo J-F, Hoke CH Jr, 2001. Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers. Vaccine 19 :3179–3188.

    • Search Google Scholar
    • Export Citation
  • 8

    Hoke CH Jr, Malinoski FJ, Eckels KH, Scott RM, Dubois DR, Summers PL, Simms T, Burrous J, Hasty SE, Bancroft WH, 1990. Preparation of an attenuated dengue 4 (341750 Carib) virus vaccine. II. Safety and immunogenicity in humans. Am J Trop Med Hyg 43: 219–226.

    • Search Google Scholar
    • Export Citation
  • 9

    Edelman R, Tacket CO, Wasserman SS, Vaughn DW, Eckels KH, Dubois DR, Summers PL, Hoke CH Jr, 1994. A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans. J. Infect Dis 170 :1448–1455.

    • Search Google Scholar
    • Export Citation
  • 10

    Innis BL, Eckels KH, Kraiselburd E, Dubois DR, Meadors GF, Gubler DJ, Burke DS, Bancroft WH, 1988. Virulence of a live dengue virus vaccine candidate: A possible marker of dengue virus attenuation. J Infect Dis 158 :876–880.

    • Search Google Scholar
    • Export Citation
  • 11

    Bancroft WH, Top FH Jr, Eckels KH, Anderson JH Jr, McCown JM, Russell PK, 1981. Dengue-2 vaccine: Virological, imunological, and clinical responses of six yellow fever-immune recipients. Infect Immun 31 :698–703.

    • Search Google Scholar
    • Export Citation
  • 12

    Scott R M, Eckels KH, Bancroft WH, Summers PL, McCown JM, Anderson JH, Russell PK, 1983. Dengue 2 vaccine: dose response in volunteers in relation to yellow fever immune status. J Infect Dis 148: 1055–1060.

    • Search Google Scholar
    • Export Citation
  • 13

    Bancroft WH, Scott RM, Eckels KH, Hoke CH Jr, Simms TE, Jesrani KDT, Summers PL, Dubois DR, Tsoulos D, Russell PK, 1984. Dengue virus type 2 vaccine: reactogenicity and immunogenicity in soldiers. J Infect Dis 149 :1005–1010.

    • Search Google Scholar
    • Export Citation
  • 14

    Eckels KH, Scott RM, Bancroft WH, Brown J, Dubois DR, Summers PL, Russell PK, Halstead SB, 1984. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. V. Human response to immunization with a candidate vaccine prepared in fetal rhesus lung cells. Am J Trop Med Hyg 33 :684–689.

    • Search Google Scholar
    • Export Citation
  • 15

    McKee KT Jr, Bancroft WH, Eckels KH, Redfield RR, Summers PL, Russell PK, 1987. Lack of attenuation of a candidate dengue 1 vaccine (45AZ5) in human volunteers. Am J Trop Med Hyg 36 :435–442.

    • Search Google Scholar
    • Export Citation
  • 16

    Clarke DH, Cassals J, 1958. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med Hyg 7 :561–573.

    • Search Google Scholar
    • Export Citation
  • 17

    Innis BL, Nisalak A, Nimmannitya S, Kusalertchariya S, Chongsawardi V, Suntayakorn S, Puttsiri P, Hoke CH Jr, 1989. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 40 :418–427.

    • Search Google Scholar
    • Export Citation
  • 18

    Russell PK, Nisalak A, Sukhavachana P, Vivona S, 1967. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol 99: 285–290.

    • Search Google Scholar
    • Export Citation
  • 19

    Yuill TM, Sukhavachana P, Nisalak A, Russell PK, 1968. Dengue-virus recovery by direct and delayed plaques in LLC-MK2 cells. Am J Trop Med Hyg 17: 441–448.

    • Search Google Scholar
    • Export Citation
  • 20

    Houng HS, Chung-Ming Chen R, Vaughn DW, Kanesa-thasan N, 2001. Development of a fluorogenic RT-PCR system for quantitative identification of dengue virus serotypes 1–4 using conserved and serotype-specific 3′noncoding sequences. J Virol Methods 95 :19–32.

    • Search Google Scholar
    • Export Citation
  • 21

    Wu S-JL, Grouard-Vogel G, Sun W, Mascola JR, Brachtel E, Putvatana R, Louder MK, Filgueira L, Marovich MA, Wong HK, Blauvelt A, Murphy GS, Robb ML, Innis BL, Birx DL, Hayes CG, Frankel SS, 2000. Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6 :816–820.

    • Search Google Scholar
    • Export Citation
  • 22

    Halstead SB, 1974. Etiologies of the experimental dengues of Siler and Simmons. Am J Trop Med Hyg 23 :974–982.

  • 23

    Simmons JS, St. John JH, Reynolds FHK, 1931. Experimental studies of dengue. Philippine J Sci 44 :1–252.

  • 24

    Moss-Blundell AJ, Bernstein S, Shepherd WM, Langford DT, Ferris R, Kelly A, 1981. A clinical study of stabilized 17D strain live attenuated yellow fever vaccine. J of Biol Stand 9:445–452.

    • Search Google Scholar
    • Export Citation
  • 25

    Guzman MG, Kouri G, Bravo J, Soler M, Vazquez S, Morier L, 1990. Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study. Am J Trop Med Hyg 42 :179–184.

    • Search Google Scholar
    • Export Citation
  • 26

    Seager C, Moriarity J, Ngai A, Staehle BO, Nalin DR, 1994. Low incidence of adverse experiences after measles or measles-rubella mass revaccination at a college campus. Vaccine 12 :1018–1020.

    • Search Google Scholar
    • Export Citation
  • 27

    Watson B, Boardman C, Laufer D, Piercy S, Tustin N, Olaleye D, Cnaan A, Starr SE, 1995. Humoral and cell-mediated immune responses in healthy children after one or two doses of varicella vaccine. Clin Infect Dis 20 :316–319.

    • Search Google Scholar
    • Export Citation
  • 28

    Wisseman CL Jr, Sweet BH, 1962. Immunological studies with Group B arthropod-borne viruses. III. Response of human subjects to revaccination with 17D strain yellow fever vaccine. Am J Trop Med Hyg 11 :570–575.

    • Search Google Scholar
    • Export Citation
  • 29

    Linnemann CC Jr, Dine MS, Bloom JE, Schiff GM, 1972. Measles antibody in previously immunized children. Am J Dis Child 124 :53–57.

  • 30

    Dittmar D, Castro A, Haines H, 1982. Demonstration of interference between dengue virus types in cultured mosquito cells using monoclonal antibody probes. J Gen Virol 59 :273–282.

    • Search Google Scholar
    • Export Citation
  • 31

    Sabin AB, 1962. Oral poliovirus vaccine. Recent results and recommendations for optimal use. J R Soc Health J 82 :51–58.

  • 32

    Sabin AB, 1952. Research on dengue in World War II. Am J Trop Med Hyg 1 :30–50.

  • 33

    Sardelis MR, Edelman R, Klein TA, Innis BL, Putnak JR, Jones JW, Turell MJ, 2000. Limited potential for transmission of live dengue virus vaccine candidates by Aedes aegypti and Aedes albopictus.Am J Trop Med Hyg 62 :698–701.

    • Search Google Scholar
    • Export Citation
  • 34

    Halstead SB, Palumbo NE, 1973. Studies on the immunization of monkeys against dengue. II. Protection following inoculation of combinations of viruses. Am J Trop Med Hyg 22 :375–381.

    • Search Google Scholar
    • Export Citation
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