SEROTYPE-SPECIFIC TH1 RESPONSES IN RECIPIENTS OF TWO DOSES OF CANDIDATE LIVE-ATTENUATED DENGUE VIRUS VACCINES

WILLIAM GWINN Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

Search for other papers by WILLIAM GWINN in
Current site
Google Scholar
PubMed
Close
,
WELLINGTON SUN Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

Search for other papers by WELLINGTON SUN in
Current site
Google Scholar
PubMed
Close
,
BRUCE L. INNIS Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

Search for other papers by BRUCE L. INNIS in
Current site
Google Scholar
PubMed
Close
,
JEFFREY CAUDILL Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

Search for other papers by JEFFREY CAUDILL in
Current site
Google Scholar
PubMed
Close
, and
ALAN D. KING Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

Search for other papers by ALAN D. KING in
Current site
Google Scholar
PubMed
Close
Restricted access

As part of a larger vaccine study, peripheral blood mononuclear cells (PBMC) were collected from volunteers for analysis of vaccine- induced T cell responses. The PBMC were re-stimulated in vitro with live dengue virus and assayed for Th1 or Th2 memory cell responses. Re-stimulated PBMC from the volunteers predominantly secreted interferon-γ. Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a Th1 type of T cell response. The interferon-γ response was primarily serotype-specific with some serotype cross-reactivity. T cell depletion studies showed that the interferon-γ was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes. CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes. However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes. In summary, an antigen-specific Th1 type T cell response was seen as a response to vaccination using live attenuated dengue virus.

Author Notes

  • 1

    Vaughn DW, Hoke CH Jr, Yoksan S, LaChance R, Innis BL, Rice RM, Bhamarapravati N, 1996. Testing of a dengue 2 live-attenuated vaccine (strain 16681 PDK 53) in ten American volunteers. Vaccine 14 :329–336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Edelman R, Tacket CO, Wasserman SS, Vaughn DW, Eckels KH, Dubois DR, Summers PL, Hoke CH, 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Mosmann TR, 1986. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136 :2348–2357.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Peters M, 1996. Actions of cytokines on the immune response and viral interactions: an overview. Hepatology 23 :909–916.

  • 7

    Conrad DH, Ben-Sasson SZ, Le Gross G, Finkleman FD, Paul WE, 1990. Infection with Nipostrongylus braziliensis.J Exp Med 171 :1497–1508.

  • 8

    Pacsa AS, Agarwal R, Elbishbishi EA, Chaturvedi UC, Nagar R, Mustafa AS, 2000. Role of interleukin-12 in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol 28 :151–155.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Kurane I, Innis BL, Nimmannitya S, Nisalak A, Meager A, Janus J, Ennis FA, 1991. 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. J Clin Invest 88 :1473–1480.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Johnson AJ, Roehrig JT, 1999. New mouse model for dengue virus vaccine testing. J Virol 73 :783–786.

  • 11

    Kontny U, Kurane I, Ennis FA, 1988. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells. J Virol 62 :3928–3933.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Sittisombut N, Maneekarn N, Kanjanahaluethai A, Kasinrerk W, Viputtikul K, Supawadee J, 1995. Lack of augmenting effect of interferon-gamma on dengue virus multiplication in human peripheral blood monocytes. J Med Virol 45 :43–49.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Kurane I, Brinton MA, Samson AL, Ennis FA, 1991. Dengue virus-specific, human CD4+ CD8- cytotoxic T-cell clones: multiple patterns of virus cross-reactivity recognized by NS3-specific T-cell clones. J Virol 65 :1823–1828.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Kurane I, Rothman AL, Livingston PG, Green S, Gagnon SJ, Janus J, Innis BL, Nimmannitya S, Nisalak A, Ennis FA, 1994. Immunopathologic mechanisms of dengue hemor-rhagic fever and dengue shock syndrome. Arch Virol (suppl) 9 :59–64.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Dharakul T, Kurane I, Bhamarapravati N, Yoksan S, Vaughn DW, Hoke CH, Ennis FA, 1994. Dengue virus-specific memory T cell responses in human volunteers receiving a live attenuated dengue virus type 2 candidate vaccine. J Infect Dis 170 :27–33.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Kurane I, Meager A, Ennis FA, 1989. Dengue virus-specific human T cell clones. Serotype crossreactive proliferation, interferon gamma production, and cytotoxic activity. J Exp Med 170 :763–775.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Kurane I, Innis BL, Hoke CH Jr, Eckels KH, Meager A, Janus J, Ennis FA, 1995. T cell activation in vivo by dengue virus infection. J Clin Lab Immunol 46 :35–40.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 868 816 52
Full Text Views 484 15 2
PDF Downloads 102 18 2
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save